This study explores the efficacy of antimicrobial preservatives in topical gels, following European Pharmacopoeia guidelines and Hungarian national formulary standards. Results indicate that benzoic and sorbic acid salts exhibit significant antimicrobial activity, making them promising alternatives to parabens. However, zinc gluconate and ethanolic solutions of methyl paraben showed limited efficacy. Surprisingly, the choice of gelling agent did not significantly affect the effectiveness of the tested materials. Overall, the study contributes to enhancing the safety and efficacy of external pharmaceutical formulations by addressing concerns about preservative toxicity and ensuring microbial stability throughout product shelf life.