Abstract The manufacturing of orange juice generates high volumes of orange peel waste which should not be deposited in landfill according to current recommendations. Furthermore, glycerol is a compound co-generated in biodiesel manufacturing, but the volume generated is higher than the current demand for pure glycerol. The anaerobic co-digestion of orange peel waste with residual glycerol could reduce the inhibitory effect of some compounds and provide a correct nutrient balance. Under mesophilic temperature and semi-continuous conditions, a mixture of orange peel waste-residual glycerol of 1:1 (in COD) operated favorably for organic loads up to 2.10g VS/L. At higher organic loads, the accumulation of volatile fatty acids (VFA) and a decrease in the pH caused process destabilization. The methane yield coefficient was quite constant, with a mean value of 330±51mLSTP/gVSadded, while the organic loading rate (OLR) reached a mean value of 1.91±0.37kgVS/m3d (17.59±2.78kgmixture/m3d) and the hydraulic retention time (HRT) varied in a range of 8.5–30.0 d.