Plants from the genus Salvia are used in traditional medicine worldwide and are considered a source of biologically active compounds due to the isolation of a diverse array of molecular skeletons, including terpenoids and polyphenols. Salvia melissodora is endemic to Mexico, occurring across the states of Aguascalientes, Durango, Guanajuato, Jalisco, Michoacán, Oaxaca, Puebla, and Querétaro, and is included in several ethnopharmacopeas from Mexico, highlighting its medicinal potential for treating respiratory and digestive afections, among others. The literature reports the presence of highly oxidized neoclerodane diterpenoids in S. melissodora as non-volatile metabolites, whereas caryophyllene, muurolene, spathulenol, caryophyllene oxide, and germacrene are described as the main constituents of the essential oil from aerial parts. Given these antecedents, increasing knowledge about the chemical constituents of this useful plant becomes pertinent. In the present work, the phytochemical study of the aerial parts of S. melissodora was conducted by preparative chromatography to isolate oleanolic acid, 3β-acetoxyoleanolic acid, lupeol, 3β,20,25-trihydroxylupane, 3β,20-dihydroxylupane, kerlinic acid, spathulenol, and 5,3’-dihydroxy-6,7,4’-trimethoxyflavone. All compounds were characterized by their physical and spectroscopic data. Based on the herein-isolated metabolites and the literature on their biological potential, a partial association between the ethnopharmacological use of S. melissodora in Mexico and its chemical constituents could be suggested, thereby complementing previously reported accounts of this plant.