As a consequence of the alarming rise in antimicrobial resistance, this study aimed at evaluating the bioactive potential of sea urchin extract, Diadema sp. Two different tissues; shells and gonads were used and two drying methods were compared; freeze-drying (FD) and non-FD (NFD). Statistically, significant interaction was observed between the drying methods and solvents used. Compared to the gonadal tissue, NFD methanolic shell extract reported higher extraction yield, 9.13 ± 0.87%. Phenolic content assessed using the Folin-Ciocalteu method was higher in NFD gonadal extract, 688.1 mg gallic acid equivalents/g distilled water. Promising antimicrobial activity was recorded using agar disc diffusion and results confirmed using minimum inhibitory concentration. Among the bacteria used, Escherichia coli and Staphylococcus aureus were more vulnerable, reporting inhibition zone of 16.3 ± 1.37 mm and 17.1 ± 0.23 mm using NFDSM and FDGM extract, respectively. DPPH antioxidant assay showed NFDSM having better activity than the positive control, half maximal inhibitory concentration of 3.77 µg/ml. No significant larvicidal activity was recorded. Diadema sp. are a potential source of novel antimicrobial compounds and suggest its possible use as natural food-grade antioxidant. This study also shows NFD method and methanol as the recommended solvent for maximal bioactivity.