The biodegradability and toxicity of three commercial pesticides containing 2-methyl-4-chlorophenoxyacetic acid (MCPA), imidacloprid and dimethoate were evaluated individually, and a complex mixture of these pesticides was treated in an expanded granular sludge bed (EGSB) reactor. MCPA was partially biodegraded, while imidacloprid and dimethoate remained almost unaltered during the individual biodegradability tests. Cyclohexanone was identified as the major solvent in the dimethoate-bearing insecticide, which was completely removed regardless of the presence of other pesticides. The analysis of the inhibition over the acetoclastic methanogenesis showed IC50 (half maximal inhibitory concentration) values of 474 and 367 mg/L for imidacloprid and dimethoate, respectively. The effect on the methanogenesis was negligible in the case of MCPA and cyclohexanone. Pesticides caused a dramatic decrease of the EGSB reactor performance. After 30 d acclimation, the EGSB reactor achieved a stable chemical oxygen demand (COD) removal efficiency and methane production of around 85% and 0.9 g CH4-COD/g COD, respectively, for MCPA, imidacloprid, dimethoate and cyclohexanone feed concentrations of 57, 20, 25 and 27 mg/L, respectively. The presence of complex pesticide mixtures led to synergistic/antagonistic responses, reducing the MCPA biodegradation and improving the removal of the insecticides' active ingredients, which were completely removed in the EGSB reactor.