The ongoing quest for novel therapeutic agents has directed attention toward bioactive compounds derived from sponge-associated bacteria. This study focuses on sponge symbiont bacteria from the mangrove ecosystems in Tanjung Tiram, Southeast Sulawesi, which have not yet been reported for their potential antibacteria, anti-inflammatory, antioxidant, and anti-diabetic activities. The screening of marine bacterial isolates was performed using a series of assays: disc diffusion method to assess antibacterial activity, protein denaturation to assess anti-inflammatory properties, DPPH free radical scavenging to evaluate antioxidant capacity, and α-Glucosidase inhibition for anti-diabetic activity, followed by in silico validation. Two promising strains, identified through molecular techniques were designated as Oceanimonas sp. JM-AZM31 and Lysinibacillus fusiformis JM-AZM37. Initial bioactivity screening revealed significant potential: The bacterial isolates JM-AZM31 and JM-AZM37 demonstrated broad-spectrum antibacterial activity against both Gram-positive pathogens (Bacillus cereus, Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative pathogens (Escherichia coli, Salmonella typhimurium). JM-AZM31 exhibited an anti-inflammatory inhibition rate of 76.9 ± 2.90 %, antioxidant activity of 80.3 ± 1.02 %, and anti-diabetic activity of 84.9 ± 0.49 %. Similarly, JM-AZM37 showed anti-inflammatory activity of 71.6 ± 1.85 %, antioxidant activity of 76.9 ± 0.03 %, and anti-diabetic activity of 83.2 ± 1.27 %. Further analysis using GC-MS identified five significant compounds, which were examined through in silico molecular docking. Results indicated that n-hexadecanoic acid, DL-proline, 5-oxo-, and cis-vaccenic acid showed high binding affinities to specific therapeutic targets, suggesting strong potential as biotherapeutic agents. This current inquiry concentrates on the therapeutic potential of marine bacteria from mangrove ecosystems as a source of bioactive compounds, positioning Oceanimonas sp. JM-AZM31 and L. fusiformis JM-AZM37 as promising candidates for developing new biotherapeutic treatments.