We established a generalized tight-binding method (TBM) to study the coupling effects in metamaterials. All parameters involved in our theory can be calculated from first principles, and the theory is applicable to general photonic systems with both dielectric and magnetic materials. As an illustration, we applied the theory to study the cutoff waveguides loaded with resonant electric/magnetic metamaterials. We not only accurately computed the coupling strengths between two resonant metamaterials, but also revealed a number of interesting coupling-induced phenomena. Microwave experiments and full-wave numerical simulations were performed to successfully verify all predictions drawn from the TBM.