The microbial contamination in food packaging has been a major concern that paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of a-mangostin (I) by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher bactericidal activity than the parent molecule. The anti-microbial studies proved that II showed high anti-bacterial activity whereas III showed the highest anti-fungal activity. Due to their microbicidal potential, modified a-mangostin derivatives could be utilized as active anti-microbial agents in materials for the biomedical and food industry.