Obesity is associated with a decrease in chemosensory perception acuity and increased disease risk, pointing to the need for feasible interventions that affect smell, taste, and cardiometabolic markers. Here, subjects with overweight/obesity are treated with six monthly cycles of a fasting-mimicking diet (FMD) lasting 5 days followed by a normal diet for the rest of the month to determine their effects on chemosensory function and cardiometabolic risk factors. Both arms of the 102 randomized cross-over trial participants indicate FMD-dependent improvements in a wide range of taste and smell chemosensory functions. The portion of hyposmic subjects is reduced from 38.1% at baseline to 6.4% at the end of 6 FMD cycles. FMD cycles also reduce cardiometabolic and inflammatory markers and drug use in diabetic patients. This trial provides evidence for the effect of periodic FMD cycles in improving chemosensory function while reducing cardiometabolic risk factors without requiring long-term lifestyle changes. The trial is registered at ClinicalTrials.gov (NCT04529161).