The study investigates the effect of the oxidant calcium oxide (CaO) on the codigestion of excess sludge (ES) and plant waste (PW) under mesophilic anaerobic conditions to enhance methane production. The findings indicate that CaO significantly elevated methane yield in the codigestion system, with an optimum CaO addition of 6% resulting in a maximum methane production of 461 mL/g volatile solids, which is approximately 1.3 times that of the control group. Mechanistic exploration revealed that CaO facilitated the disintegration of organic matter, enhanced the release of soluble chemical oxygen demand, and increased the concentrations of soluble proteins and polysaccharides within the codigestion substrate. The presence of CaO was conducive to the generation and biological transformation of volatile fatty acids, with a notable accumulation of acetic acid, a smaller carboxylic acid within the VFAs. The proportion of acetate in the CaO-amended group increased to 32.6-36.9%. Enzymatic analysis disclosed that CaO enhanced the activity of hydrolytic and acidogenic enzymes associated with the ES and PW codigestion process but suppressed the activity of coenzyme F420. Moreover, CaO augmented the nutrient load in the fermentation liquid. The study provides an alternative scheme for the efficient resource utilization of ES and PW.