Medicinal plants are known by pharmacological relevance and were used for long time to prevent/treat numerous gastrointestinal (GI) disorders. The current study focuses on the phytochemical/antioxidant characteristics of sage aqueous extract (SAE), as well as its pharmacological actions on altering motor function in the intestine and related disruptions. In vitro phytochemical/antioxidant properties were investigated by colorimetric/biochemical methods. Male rats were divided into seven groups of six animals in each: control (C), castor oil (CO), CO + loperamide (LOP, 10 mg/kg, b.w., p.o.), CO + various doses of SAE (50, 100, and 200 mg/kg, b.w., p.o.), and the mixture (MIX: SAE, 50 mg/kg, b.w., p.o. + LOP, 5 mg/kg, b.w., i.p.) group. In vivo GI/physiological/pharmacological actions of SAE were explored based on the watery/frequent stools, enteropooling, and GI transit time, as well as their associated disturbances. The aqueous extract of S. officinalis contains high tannins/flavonols/anthocyanin contents and a strong, free radical scavenging activity (EC₅₀ = 48.56 ± 0.34 μg/mL). SAE/MIX significantly reduced CO-induced diarrhea in a dose-dependent manner. SAE/MIX decreased also the gastric and intestinal mucosal malondialdehyde/hydrogen peroxide levels and preserved the normal activities/levels of enzymatic/nonenzymatic antioxidants. Added to that, we showed that SAE/MIX pretreatment provided stability of lipid profile (cholesterol and triglycerides), hepatic transaminases, renal injury indicators, and C-reactive protein/alkaline phosphatase levels changed by CO intoxication. These findings suggested that SAE/MIX exerted benefic individual/synergistic effects confirming their use as a strategy in the treatment of GI physiological disorders.