Nutritive sweeteners (NS) contribute to overall caloric intake, and their adverse effects on metabolic health are well known. Non-nutritive sweeteners (NNS) on the other hand, have negligible or no calorific value and are therefore used as replacement of NS to negate their associated health risks. Whilst the consumption of NNS has steadily increased over the recent years, so has the evidence questioning their benefits. Some research suggesting that NNS could be an indirect contributor to the development of metabolic diseases. This review presents a brief compilation of current knowledge relating to NNS and metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease. Summarised are findings from randomised controlled trials (RCT), prospective cohort studies, observations from animal studies and recent microbiome research. The authors noted that NNS frequently exerted negative influences on health in prospective cohort studies, which observed selected population groups over time. Whilst in controlled trials, NNS often showed neutral or positive health benefits. Following a discussion of possible causes leading to such variations and conflicting outcomes, the authors called for more carefully designed studies to evaluate NNS and their metabolic influences. For clinicians, it may be worth considering further evidence relating to the individual types of sweeteners when evaluating NNS and their risks and benefits on cardiometabolic health.