Background: Recent developments on skin bioactive are heading towards utilization of inactivated bacteria (bacterial lysate), containing soluble factors potential for various modulatory effect on skin health, while offering safety advantages over viable probiotics. Several lactic acid bacteria (LAB) have been developed as bacterial lysate for skin health, e.g. Lactobacilli and Bifidobacteria. Objective: Different variables were optimized to obtain larger amount of Streptococcus macedonicus MBF 10-2 lysate, such as peptone source and cell disruption method. Antimicrobial activity, antioxidant activity, and anti-tyrosinase activity was carried out to support lysate’s potential in modulating skin health.  Materials and Methods: Fermentation of Streptococcus macedonicus MBF 10-2 was carried out in plant-based modified de Man Rogosa and Sharpe (MRS) medium in a 2L fermenter tank by previously optimized method obtained by response surface methodology (RSM). Obtained cells were lysed using ultrasonication and ultrasonication-lysozyme method. Bacterial lysate was then freeze-dried to obtain concentrated active lysate. Antimicrobial activity of lysate against standard bacteria and several skin resident bacteria was carried out using liquid microdilution method.  Antioxidant and anti-tyrosinase activity of strain MBF 10-2 was assessed. Results: MRS Soy Peptone was selected as the optimum growth media of strain MBF 10-2 due to greater amount of cell pellets obtained. Disruption of cells by ultrasonication yielded average of 10,59% freeze-dried powder from total cell mass, while ultrasonication-enzymatic method yielded average of 5,63%.  MIC of lysate against Streptococcus pyogenes, Staphylococcus epidermidis, Staphylococcus aureus, and Corynebacterium diphteriae was observed at >200,000 ppm. Conclusion: Lysate of Streptococcus macedonicus MBF 10-2 has potential effects on skin health, not only by modulatory effect on skin resident microbiota, but also by antioxidant and anti-tyrosinase activities.