Propionibacterium acnes and Staphylococcus epidermidis are Gram-positive commensal bacteria on human skin that can turn opportunistic. In a previous study, Cassia alata L. leaves extract had shown antibacterial activity against Gram-positive bacteria. In this study, C. alata leaves extract is used as an active ingredient in a topical cream preparation. This study aimed to determine the stability and the antibacterial activity of C. alata leaves extract cream against P. acnes and S. epidermidis. We prepared topical cream containing 1.25%, 2.5%, and 5% of C. alata extract and evaluated their physical parameters. The prepared C. alata leaves extract cream had good physical characteristics, but there were underwent changes during the accelerated stability test. The antibacterial activity of the C. alata leaves extract cream was studied using the agar well diffusion method. The results showed that the variations of C. alata leaves extract affected the antibacterial activity against P. acnes and S. epidermidis. Cream containing 5% ethanolic extract of C. alata leaves had the highest antibacterial activity.