In a study utilizing NMR spectroscopy and chemometrics, propolis samples from seven diverse geographic regions across Turkey were analyzed. To identify the optimal method for studying both the antimicrobial properties and compositional variations of propolis from different regions, we investigated metabolite extraction using three solvents: water only, ethanol only, and sequential water-ethanol extraction for residual components. Notably, water-soluble components exhibited significant variation among the samples, which is particularly interesting considering the potability of propolis in water-based solutions. Furthermore, the Muğla sample displayed a distinct water-soluble profile, likely due to its unique coastal location on the Aegean Sea. This specific climate may influence the propolis' chemical composition, resulting in a different mixture of components. Interestingly, the Muğla sample contained pharmaceutically active compounds like cinnamate, ferulate, and verapamil. This research establishes a valuable foundation for further exploration of propolis' antimicrobial potential.