<p>In this study, the antioxidant and antimicrobial activities, enzyme inhibition, and total phenolic and flavonoid content of extracts obtained from different plant organs (flower, stem + leaf, and root) of endemic <i>Achillea boissieri</i> and <i>Achillea cucullata</i> species naturally growing in Kahramanmaraş were investigated. Additionally, the fixed oil content of the extracts was analyzed through gas chromatography–mass spectrometry, revealing that, except for the aerial part of <i>A. cucullata</i>, all examined plant organs were rich in unsaturated fatty acids. Oleic acid, linoleic acid, and gamma-linolenic acid were identified as the main fatty-acid components of <i>A. boissieri</i>, whereas palmitic, oleic, and linoleic acid constituted the major fatty acids of <i>A. cucullata</i>. Behenic acid was the major fatty acid in the aerial parts of <i>A. cucullata</i>, accompanied by palmitic, lignoceric, and gamma-linolenic acid. The choice of extraction solvent was found to significantly affect the extraction of phenolics, flavonoids, and antioxidant activity, with methanol being more effective than ethanol. Bioactive contents in aerial parts generally showed higher levels than other organs. Furthermore, a significant positive correlation between phenolics and flavonoids was observed. The antimicrobial activity of the plant extracts was accomplished using a well diffusion method and minimum inhibitory concentration values were determined in microplates. According to the results, the extracts of <i>A. boissieri</i> and <i>A. cucullata</i> exhibited a noteworthy antibacterial and antifungal effect against the test microorganisms. In terms of solvent efficiency, the methanol produced better results than ethanol. The highest enzyme inhibitory activity was detected with methanolic extract <i>A. boissieri</i> flower (16 μg/mL).</p>