<p>The increasing demand for natural and sustainable cosmetic products has fueled interest in plant-based ingredients. Skin aging, driven by oxidative damage and enzymatic overactivation, results in wrinkles, sagging, and pigmentation disorders. The proposed study targeted radical scavenging activity and key hyperpigmentation enzymes such as tyrosinase to develop effective anti-aging and skin-whitening agents. We employed an integrated analytical approach combining high-performance thin-layer chromatography (HPTLC) with bioassays (HPTLC‒2,2-diphenyl-1-picrylhydrazyl [DPPH] and HPTLC‒tyrosinase) as an ecofriendly, rapid, and cost-effective tool for (bio)screening of natural plant extracts. The structural characterization of active compounds was further achieved using attenuated total reflectance‒Fourier transform infrared spectroscopy (ATR‒FTIR). Additionally, total phenolic and total flavonoid content were determined to assess bioactive content. Principal component analysis (PCA) enabled the classification of extracts based on their chemical signatures. Our results demonstrated that <i>Rosaceae</i> plants, including hawthorn and dog rose, exhibit promising antipigmentation properties, whereas agrimony (<i>Rosaceae</i>) and wall germander (<i>Lamiaceae</i>) showed potent antioxidative activity. The HPTLC‒DPPH-tyrosinase‒ATR‒FTIR approach proposed bioactive compounds. This integrative HPTLC approach highlights the potential of Serbian medicinal plants as sustainable sources for innovative cosmeceuticals.</p>