Sleep regularity is an essential part of the multidimensional sleep health framework. The phenomenon of irregular sleep patterns is widespread in contemporary lifestyles. This review synthesizes clinical evidence to summarize the measures of sleep regularity and discusses the role of different sleep regularity indicators in developing cardiometabolic diseases (coronary heart disease, hypertension, obesity, and diabetes). Existing literature has proposed several measurements to assess sleep regularity, mainly including the standard deviation (SD) of sleep duration and timing, sleep regularity index (SRI), interdaily stability (IS), and social jetlag (SJL). Evidence on associations between sleep variability and cardiometabolic diseases varies depending on the measure used to characterize variability in sleep. Current studies have identified a robust association between SRI and cardiometabolic diseases. In comparison, the association between other metrics of sleep regularity and cardiometabolic diseases was mixed. Meanwhile, the associations of sleep variability with cardiometabolic diseases differ across the population. SD of sleep characteristics or IS may be more consistently associated with HbA1c in patients with diabetes compared with the general population. The association between SJL and hypertension for patients with diabetes was more accordant than in the general population. Interestingly, the age-stratified association between SJL and metabolic factors was observed in the present studies. Furthermore, the relevant literature was reviewed to generalize the potential mechanisms through which irregular sleep increases cardiometabolic risk, including circadian dysfunction, inflammation, autonomic dysfunction, hypothalamic–pituitary–adrenal (HPA) axis disorder, and gut dysbiosis. Health-related practitioners should give more attention to the role of sleep regularity on human cardiometabolic in the future.