The circadian clock system orchestrates daily behavioral and physiological rhythms, facilitating adaptation to environmental and internal oscillations. Disruptions in circadian rhythms have been linked to increased susceptibility to various diseases and can exacerbate existing conditions. This review delves into the intricate regulation of diurnal gene expression and cell function by circadian clocks across diverse tissues. . Specifically, we explore the rhythmicity of gene expressions, behaviors, and functions in both immune and non-immune cells, elucidating the regulatory effects and mechanisms imposed by circadian clocks. A detailed discussion is centered on elucidating the complex functions of circadian clocks in regulating key cellular signaling pathways. We further review the circadian regulation in diverse diseases, with a focus on inflammatory diseases, cancers, and systemic diseases. By highlighting the intimate interplay between circadian clocks and diseases, especially through clock-controlled cell function, this review contributes to the development of novel disease intervention strategies. This enhanced understanding holds significant promise for the design of targeted therapies that can exploit the circadian regulation mechanisms for improved treatment efficacy.© 2024 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.