Abstract The anaerobic co-digestion of spent coffee grounds (SCG) and Ulva biomass, which are problematic wastes and unsuitable for mono-digestion, with food waste (FW) was investigated to widen the scope of feedstocks for biogas production. The effect of the feedstock mixing ratio on the methane yield and synergistic effect of co-digestion was analyzed by response surface analysis. The models for the methane yield and synergistic effect indicated different response patterns and predicted the maximum responses at different mixing ratios. As maximizing the conversion of individual feedstocks to methane is the primary focus in this study, the mixing ratio required for maximizing the synergy index is perceived to be more desirable than that for maximizing methane yield of the mixture. The experimental and modeling results demonstrated that FW, SCG, and Ulva biomass can be effectively co-digested with little antagonistic effect, regardless of their mixing ratio, and a synergistic effect in most cases. It is expected that co-digestion could be flexibly applied when managing the waste feedstocks to enhance their energy recovery potential. The findings of this study can help promote the valorization of underused waste feedstocks through co-digestion and increase the deployment of renewable energy.