Antibiotic resistance is an ever-increasing issue globally and is constantly endangering health due to potentially new threatening bacterial infections. Researchers are constantly searching for new and alternative ways to combat this issue and most often, turn to existing natural compounds to identify any pharmaceutical potential in those compounds. Capsaicin, the main capsaicinoid of the genus Capsicum, has caught research interest as a promising bioactive compound. Capsaicin is known for its antimicrobial, antifungal, anticarcinogenic, and anti-inflammatory properties depending on the dose and usage. Another known product that is commonly used is probiotics and has been a staple beneficial microbe that has existed for a long time and is known for its immunomodulatory and antimicrobial properties towards health. Capsaicin or probiotics, as standalone product, might not be effective enough to fight the increasing antibiotic resistance issue. One possible solution is to combine the two products to enhance their potential. This research experiment aims to enhance the ability of probiotic (Bifidobacterium breve) to fight pathogen, by cultivating it with a natural compound (capsaicin). The capsaicin was extracted from cayenne chili peppers (Capsicum frutescens) using physical (grinding) and chemical (solvent) extraction. Its concentration was determined using spectrophotometry at 650 nm through reaction with phosphomolybdic acid. The extracted capsaicin was incorporated into B. breve BS2-PB3 culture and was subsequently tested against Methicillin-resistant Staphylococcus aureus (MRSA). Results showed that B. breve culture with capsaicin supplementation indeed increased the clear zone diameter against MRSA in comparison to individual controls (capsaicin or B. breve). In conclusion, the results of this experiment suggested the effectiveness of combining natural compound with probiotics, as the mixture would have a stronger antimicrobial property.