Infectious diseases are disorders that can cause or transmit disease. In 2019, an estimated 13.7 million deaths came from infectious diseases, 5 bacteria that most commonly cause infectious diseases are Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Ciplukan (Physalis angulata L.) is thought to be used as an antibacterial. This study aimed to test the activity of ciplukan leaf fraction against Staphylococcus aureus and Escherichia coli. This research was conducted in August - October 2023 at 2023 at Pharmacognosy Laboratory and Microbiology Laboratory of ITSK DR. Soepraoen Hospital. This research is an experimental quantitative study with macerated ciplukan leaf samples and then continued fractionation using n-hexane, ethyl acetate, and ethanol. The antibacterial activity test used disc diffusion method with 50% DMSO negative control and 30 μg chloramphenicol positive control. Antibacterial activity is indicated by the diameter of the clear zone around the disc then the results were analysed with One Way ANOVA. The highest result antibacterial activity of 20% ethanol fraction were 8.4725 mm on Staphylococcus aureus and 11.6225 mm on Escherichia coli. In the n-hexane fraction against Escherichia coli, no antibacterial activity was found. Based on the results, it is known that the ethanol fraction of 20% concentration is the fraction that has the most effective antibacterial activity against Staphylococcus aureus and Escherichia coli. Based on One Way ANOVA test in each group of bacteria, significant differences were found. Recommended for future researchers to conduct the same research but using the well diffusion method.