Maintaining skeletal muscle functions by controlling muscle metabolism is of utmost importance. β₂-Adrenergic receptor (β₂-AR), which is expressed in skeletal muscle, is a member of the G-protein-coupled receptor family that plays a critical role in the maintenance of muscle mass. In the present study, using luciferase reporter assays in β₂-AR-expressing HEK293 cells, we discovered several food factors that exhibited agonistic activity at mouse or human β₂-AR. Osthole, gramine, and hordenine were identified as both mouse and human β₂-AR agonists, whereas berberine was identified as a mouse β₂-AR agonist only. Additionally, intramuscular injection of gramine or hordenine in mice facilitated gene expression of several cAMP response element binding protein targets, which is thought to result in increased skeletal muscle protein synthesis. This study provides evidence that several food factors might exert potential health effects on skeletal muscle by enhancing cAMP signaling through the activation of β₂-AR.