Objective: To determine the seasonal and geographical impact on plant secondary metabolite production and antimicrobial activity. Methods: Three mangrove plants viz., Ceriops tagal, Bruguiera cylindrica and Lumnitzera racemosa commonly found in Gilakaladindi and Malakayalanka regions of Krishna Estuary, Andhra Pradesh, India were selected for the present study. The study was done during 2014-15 summer, rainy and winter in both the stations. Leaf samples were extracted with methanol and subjected to preliminary phytochemical screening. The methanolic leaf extracts were tested against bacterial pathogens Bacillus cereus, B. subtilis, Staphylococcus aureus, Escherichia coli and a fungal pathogen Candida albicans. Results: The methanolic extracts of leaves collected during rainy season showed maximum zone of inhibition at both the stations Gilakaladindi and Malakayalanka. Among the studied plants leaf methanolic extract of C.tagal was recorded maximum antibacterial activity against B. subtilis and B. cereus (18__ampersandsignplusmn;0.05 mm), followed by Bruguiera cylindrica both at Gilakaladindi and Malakayalanka respectively. But the extracts of L.racemosa showed less inhibition activity (7__ampersandsignplusmn;0.00 mm) in all the seasons at both the stations. Conclusion: The study demonstrated that mangroves produce bio-active compounds optimally in rainy season that are effective against microbial proliferation which may further help in synthesis of natural antibiotics in place of commercial antibiotics to heal infectious diseases.