This study aimed to evaluate the antidepressant-like effects of aqueous extracts of miswak (Salvadora persica) and date palm (Phoenix dactylifera) and their combination on depression-like behaviors using a chronic unpredictable mild stress (CUMS) rat model of depression and to investigate the underlying possible mechanisms. Resultsshowed that CUMS induced depression-like behaviors and anxiety in male rats, as determined by behavioral tests (FST, EPM, and OFT). CUMS significantly increased the How to cite this article: Youssef, B., Ramadan, K. S., ElShebiney, S. & Ibrahim, E. A. (2022). Antidepressant-like effects of aqueous extracts of miswak (Salvadora persica) and date palm (Phoenix dactylifera) on depression-like behaviors using CUMS model in male rats.