In this study, the leaves ofKalanchoe fedtschenkoiwere consecutively macerated with hexane, chloroform, and methanol. These extracts were used to assess the bioactivities of the plant. The antimicrobial activity was tested against a panel of Gram-positive and -negative pathogenic bacterial and fungal strains using the microdilution method. The cytotoxicity ofK. fedtschenkoiextracts was investigated using human-derived macrophage THP-1 cells through the MTT assay. Finally, the anti-inflammatory activity of extracts was studied using the same cell line by measuring the secretion of IL-10 and IL-6. The phytoconstituents of hexane and chloroform extracts were evaluated using gas chromatography–mass spectrometry (GC/MS). In addition, high-performance liquid chromatography (HPLC) was used to study the phytochemical content of methanol extract. The total flavonoid content (TFC) of methanol extract is also reported. The chemical composition ofK. fedtschenkoiextracts was evaluated using Fourier-transform infrared spectroscopy (FTIR). Results revealed that the chloroform extract inhibited the growth ofPseudomonas aeruginosaat 150μg/mL. At the same concentration, methanol extract inhibited the growth of methicillin-resistantStaphylococcus aureus(MRSA). Regarding their cytotoxicity, the three extracts were highly cytotoxic against the tested cell line at IC50< 3μg/mL. In addition, the chloroform extract significantly stimulated the secretion of IL-10 at 50μg/mL (p< 0.01). GC/MS analyses revealed that hexane and chloroform extracts contain fatty acids, sterols, vitamin E, and triterpenes. The HPLC analysis demonstrated that methanol extract was constituted by quercetin and kaempferol derivatives. This is the first report in which the bioactivities and chemical profiles ofK. fedtschenkoiare assessed for non-polar and polar extracts.