Andrographolide, a bioactive compound from Andrographis paniculata, has gained attention for its antimicrobial properties, which include antibacterial, antiviral, antifungal, and antiprotozoal effects. As an herbal extract used in traditional medicines, andrographolide also shows promise for developing new antimicrobial agents, especially in the fight against rising antimicrobial resistance. Following the PRISMA 2020 guidelines, 16 peer-reviewed studies published from 2010 to 2024 and focusing on andrographolide's effects on bacteria, viruses, fungi, and protozoa were reviewed. The quality and bias risk of these studies were assessed using the In Vitro Quality Evaluation Instrument to ensure methodological rigor. The findings demonstrate that andrographolide is effective against bacteria such as Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. However, its antifungal efficacy is limited, as it was ineffective against Candida albicans and Saccharomyces cerevisiae, but effective against Alternaria solani. It exhibited strong antiviral activity against 2019-nCoV, Dengue virus, and Enterovirus D68, and showed antiprotozoal effects against Plasmodium falciparum and Setaria cervi. Nonetheless, variations in its efficacy across different microorganisms were observed. The quality assessment revealed low bias risk in 11 out of 16 studies (78.57% to 92.86%), while the remaining five had medium bias risk (57.14% to 64.29%), indicating an overall acceptable quality of the studies. Information on andrographolide's potential and effectiveness across various microorganisms is crucial. Therefore, the purpose of this review was to synthesize the existing data on andrographolide's antimicrobial activity and assess its potential in combating antimicrobial resistance. This review highlights the need for further research on andrographolide's antifungal activity, mechanisms of action, clinical safety, toxicity, and potential applications in antimicrobial resistance strategies.