This study aimed to evaluate an activated sludge system as a post‐treatment step of anaerobic effluents from the co‐digestion of sugarcane vinasse and hemicelluloses hydrolysate. The system consisted, initially, of a two‐stage anaerobic system followed by a continuously fed activated sludge, all in bench scale. After adaptation of aerobic microorganisms to effluent conditions, the anaerobic digestion was conducted in a single‐stage anaerobic reactor, increasing the influent organic loading rate (OLR) of activated sludge from 0.73 to an average of 2.36 gCOD/L·day. Under optimal conditions (12‐h hydraulic retention time [HRT]), a 62 ± 9% efficiency was observed on the aerobic post‐treatment, resulting in effluent chemical oxygen demand (COD) of 414.3 ± 95 mg/L. Overall efficiency of the combined system (anaerobic + aerobic) averaged 88 ± 3%. Influent and effluent characteristics were then analyzed by Folin‐Ciocalteau method, UV–Vis spectrophotometry, and gas chromatography–mass spectrometry (GC–MS) for identification of potentially toxic and recalcitrant compounds. Compounds that absorb light within the visible spectra were well removed by the combined treatment system. Most compounds identified by GC–MS in the influent were completely removed by aerobic microorganisms. Saturated fatty acids such as adipic acid, hexadecanoic acid, and octadecanoic acid were observed in the final effluent, as well as other potentially toxic compounds such as stigmasterol, di‐isobutyl phthalate, and benzene. Activated sludge proved to be an efficient post‐treatment for anaerobic co‐digestion, able to cope with changes of anaerobic effluent quality and providing a final effluent of stable organic load. However, phenol removal was not efficient and further studies could be performed to optimize its degradation. Practitioner Points Conventional activated sludge with a 12‐h HRT was capable of handling significant OLR variation, providing a final effluent with lower and stable COD concentration. Glucose addition for carbon supplementation was necessary during the start‐up of activated sludge. Compounds that absorb light within the visible spectra were mostly removed by the combined (anaerobic–aerobic) treatment system. Most potentially toxic compounds were well removed in the post‐treatment system. Saturated fatty acids, VFA, phenols, and low molecular weight aromatic compounds remained in the final effluent.