The current research is dedicated to the creation of a pediatric cough syrup formula with less synthetic preservatives based on the usage of natural antimicrobial agents. The use of synthetic preservatives in pediatric formulations e.g. sodium benzoate in excess amount leads to concerns about possible toxicity and hypersensitivity. To resolve this, a control syrup that had standard concentration of sodium benzoate (0.1) was used as a control group compared with an optimized formulation that had low concentration (0.03) of sodium benzoate with added honey, clove oil and citric acid. The recipes were tested in terms of physicochemical stability, antimicrobial activity and sensorial properties within 90 days. The challenge testing with the Escherichia coli, Bacillus subtilis, Candida albicans and Aspergillus niger showed successful inhibition of microbial growth by the natural-based preservative system similar to the synthetic preservative. Physicochemical characteristics, such as pH, viscosity, color, odor, and taste were at acceptable pharmacopeial values and this means that they were stable and palatable. Statistical analysis also established there was no significant difference (p less than 0.05) in formulations in microbial reduction and stability performance. The findings indicate that the partial replacement of synthetic preservatives with natural agents is likely to increase the safety of the formulations in question without affecting its quality or effectiveness.