Nowadays there is a growing interest on the use of both lignocellulosic and algae biomass to produce biofuels (i.e. biohydrogen, ethanol and methane), as future alternatives to fossil fuels. In this purpose, thermal and thermo-chemical pretreatments have been widely investigated to overcome the natural physico-chemical barriers of such biomass and to enhance biofuel production from lignocellulosic residues and, more recently, marine biomass (i.e. macro and microalgae). However, the pretreatment technologies lead not only to the conversion of carbohydrate polymers (ie cellulose, hemicelluloses, starch, agar) to soluble monomeric sugar (ie glucose, xylose, arabinose, galactose), but also the generation of various by-products (i.e. furfural and 5-HMF). In the case of lignocellulosic residues, part of the lignin can also be degraded in lignin derived by-products, mainly composed of phenolic compounds. Although the negative impact of such by-products on ethanol production has been widely described in literature, studies on their impact on biohydrogen and methane production operated with mixed cultures are still very limited. This review aims to summarise and discuss literature data on the impact of pre-treatment by-products on H2-producing dark fermentation and anaerobic digestion processes when using mixed cultures as inoculum. As a summary, furanic (5-HMF, furfural) and phenolic compounds were found to be stronger inhibitors of the microbial dark fermentation than the full anaerobic digestion process. Such observations can be explained by differences in process parameters: anaerobic digestion is performed with more complex mixed cultures, lower substrate/inoculum and by-products/inoculum ratios and longer batch incubation times than dark fermentation. Finally, it has been reported that, during dark fermentation process, the presence of by-products could lead to a metabolic shift from H2-producing pathways (i.e. acetate and butyrate) to non-H2-producing pathways (i.e. lactate, ethanol and propionate) and whatever the metabolic route, metabolites can be all further converted into methane, but at different rates.