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Salvia circinata Cav., Lamiaceae, is commonly used in Mexican traditional medicine to treat gastrointestinal ailments, including diarrhea. An acetone-soluble extract from the aerial parts of S. circinata was suspended in a 9:1 methanol–water mixture and fractionated by partition with hexane and EtOAc. The hexane, EtOAc, and aqueous fractions were evaluated for their antiprotozoal activities, where the EtOAc-soluble fraction displayed the best antiprotozoal activity. Resolution of this fraction by chromatographic methods afforded the known diterpenoids amarissinins A–C (1–3), teotihuacanin (4), and amarisolide F (5), along with two flavones, apigenin (6) and 5,6-dihydroxy-7,3′,4′-trimethoxy flavone (7). Compound 7 was the most active one, with IC50 values of 0.05 μM and 0.13 μM against Entamoeba histolytica and Giardia lamblia, respectively. Interestingly, it was even more active than metronidazole and emetine, used as positive controls. Compounds 1–6 showed moderate antiprotozoal activity with IC50 values ranging from 23.9 to 67.8 μM against Entamoeba histolytica, and 39.4 to 127 μM against Giardia lamblia. These results provide evidence-based support for the traditional use of S. circinata, and suggest that the 5,6-dihydroxy-7,3′,4′-trimethoxy flavone (7) may have an important role in the antidiarrheal activity of the plant.