Aspartame [E951] is a white, odourless, crystalline, artificial, non-saccharide sweetener. It is composed of two amino acids, L-aspartic and L-phenylalanine acid. It is a methyl-ester of phenylalanine and aspartic acid. It is an intensely sweet powder with a molecular formula [C14H18N2O5] and a molar mass of 294.31 g mol − 1. The density of aspartame is 1.347 g/L. Aspartame is approx. 200 times sweeter than sucrose and is readily dissolvable in water. Primarily used as a sugar substitute in many foods and beverages with the brand names NutraSweet, Equal, and Canderel. Its intake was expected to reduce obesity rates in developing countries and help those with diabetes. Although not replaced, aspartame is being aggressively used instead of conventional sugars [150]. Aspartame became popular because of its reduced costs, low caloric intake, attractive advertisements and promise to contribute to weight loss. Aspartame is increasingly included in commonly consumed foods such as diet sodas, cereals, and sugar-free desserts. It is recommended for weight loss in individuals suffering from glucose intolerance and type 2 diabetes mellitus, but it has not been limited to diabetic patients only. Instead, the spectrum of use has increased widely over the last decade. It is recommended for weight loss in individuals suffering from glucose intolerance and obese people. Because of the commercial marketing strategies of food industry-related companies, the role of artificial sweeteners has been changed from sugar substitutes to healthy substitutes. Foods containing artificial sweeteners are sold as better healthy alternatives to sugar for the diabetic population and people trying to keep fit. Aspartame helps limit sucrose intake by substituting sugar and releasing meagre energy. It is metabolized more slowly than sucrose, stabilizing levels of blood sugar. Individuals with reactive hypoglycaemia produce excess insulin after quickly absorbing glucose into the bloodstream [15]. Like diabetes, high-glycaemic food avoidance often forces them to choose artificial sweeteners as an alternative. Due to this virtue, aspartame is recommended as a sugar-free medicine to most patients whenever possible [94]. Also, sucrose promotes tooth decay since bacteria naturally occurring in the human oral cavity can efficiently use sucrose as a food source, releasing waste that degrades enamel. Unlike sucrose, the microflora in the dental plaque does not utilize Aspartame [93]. For all these reasons, aspartame is increasingly and rapidly being introduced into commonly consumed food products, including diet sodas, cereals, sugar-free desserts, yoghurt, chewing gums, syrups, mouth fresheners, candies, health drinks, and many other nutritional supplements. Since as mentioned the use of non-nutritional sweeteners has not been restricted to diabetic people but has also been widely used in food edibles consumed daily by a vast population of healthy individuals. We are likely consuming these sweeteners at concentrations higher than regulatory authorities recommend. For instance, in India, the average amounts of saccharin, which is another type of NNS, in many edibles like crushed ice and ice candy samples were 24,300 and 12750 mg kg-1, respectively, which are 3- and 1.6-fold higher in dosage than the permitted maximum levels allowed by the Prevention of Food Adulteration [PFA] Act of India [152]. Likewise, People are likely to consume aspartame at a higher dosage than the recommended. Although there is limited evidence, various studies suggest several potential mechanisms through which aspartame may contribute to immune dysfunction. These mechanisms include disrupting the bidirectional communication among neuro-immune-endocrine responses, perturbing the balance of the brain-gut-microbiota-immune axis, inducing oxidative stress in immune cells and organs, and activating the immune system via methanol exposure [37]. This suggests that beyond its known neurotoxic effects on neurons, aspartame could exacerbate cognitive impairment by instigating chronic inflammation in microglial cells. Given that both aspartame consumption [54], [113] and microglial inflammation have been linked to cognitive dysfunction [46]. There remains a strong need to explore the intricate relationship between aspartame-induced microglial inflammation and cognitive decline. Further investigation is required to elucidate the potential links between aspartame consumption, ecotoxicity, and microglia-mediated inflammatory cognitive impairment. This makes it very important to understand the effects of aspartame on different human health parameters, particularly its potential role in microglia neuroinflammation because of its reported effects on neuro-cognitive health. Aspartame might affect the neurophysiological and neurobehavioral aspects by inducing inflammation in the glial population of cells, particularly microglia. Inquiring into a connection between there by incorporating a therapeutic supplementation approach is paramount to addressing cognitive concerns, given the widespread consumption globally, predominantly among the ageing population predisposed to cognitive deficits. We must integrate this approach into our study to fortify its relevance and contribute substantively to addressing this issue.