Although it has been shown that host health, circadian signaling, and the microbiome are tightly connected, the mechanistic links remain unclear. We identified a bile acid metabolite, lithocholic acid (LCA), as a circadian modulator by screening a focused library of gut microbial metabolites. Out of the larger class of compounds, LCA, and to a lesser extent isoLCA, uniquely lengthened the circadian period of hPer2 transcription in a dose-responsive manner in human colonic cells. LCA modulated the casein kinase 1 / (CK1/)-protein phosphatase 1 (PP1) feedback loop and stabilized core clock protein cryptochrome 2 (CRY2). Furthermore, we showed that LCA feeding alters circadian transcription in mouse colons. Thus, our work identifies LCA as an endogenous molecular link between host circadian biology and the microbiome, providing a new avenue to examine host health.