Lignocellulosic biomass is a renewable feedstock for second-generation bioethanol production. However, pretreatment processes produce various inhibitory compounds, primarily weak organic acids, furan derivatives, and phenolics, resulting from the breakdown of cellulose, hemicellulose, and lignin during thermochemical pretreatment. The profiles of these compounds depend on factors such as feedstock type, catalyst, temperature, and residence time. These potent inhibitors can significantly impede both enzymatic hydrolysis and yeast fermentation, even at low concentrations, thereby reducing efficiency and ethanol yield. Consequently, these inhibitors pose a significant challenge to the commercialization of cellulosic ethanol. Developing effective detoxification methods is crucial for enhancing the economic viability of lignocellulosic biorefineries. A combination of physical, chemical, and biological approaches, including engineered tolerant strains, is now commonly used worldwide as detoxification strategies to mitigate these effects, balancing efficiency, cost, and proper sugar preservation.