The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains 24 and directs oscillations through transcriptional and translational feedback loops, which modulates an 25 approximately 24 hour cycle of endocrine and metabolic rhythms within cells and tissues. While circadian 26 clocks regulate metabolic processes and related physiology, emerging evidence indicates that metabolism 27 and circadian rhythm are intimately intertwined. In this review, we highlight the concept of metabolites, 28 including lipids and other polar metabolites generated from intestinal microbial metabolism and nutrient 29 intake, as circadian pacemakers that drive changes in circadian rhythms, which in turn influence metabolism 30 and aging. Furthermore, we discuss the roles of functional metabolites as circadian pacemakers, paving a 31 new direction on potential intervention targets of circadian disruption, pathological aging, as well as 32 metabolic diseases that are clinically important.