Detoxification of inhibitory compounds in pretreated lignocellulose feedstock is a crucial step prior to consequent fermentations in the biorefinery chain. Biological detoxification offers a fast and highly selective method for biodegradation of inhibitory compounds into CO 2 and water. This study focused on the enhanced online monitoring of the end point of the submerged liquid biodetoxification by Paecilomyces variotii FN89 in high solids loading wheat straw hydrolysate. Submerged liquid biodetoxification reduces reactor volume and improves mass transfer with greater ease of operation but faces the challenge of timely switching of the biodetoxification stage into the fermentation stage of biodetoxification microbes in the lignocellulose hydrolysate with highly concentrated sugars and inhibitors. In other words, the challenge is to quickly identify the end point of biodetoxification to ensure a timely completion of inhibitors while maintaining the fermentable sugars untouched. The inadequate biodetoxification results in poor fermentability in the subsequent bioconversion step, while excessive biodetoxification leads to the unwanted consumption of fermentable sugars. The results indicate that all furfural and 5-hydroxymethylfurfural (HMF) and over 80% of acetic acid in the wheat straw hydrolysate were effectively removed within a short period (12−24 h) under moderate operating parameters and negligible loss of fermentable sugars (below 2%). We observed that the change of pH value had a certain regularity and exactly corresponded to the biodetoxification process due to the consumption of inhibitory acids (acetic acid) and the generation of acidic byproducts (fatty acids). Upon reaching the maximum pH value through the visible online observation, the biodetoxification stage could be promptly transitioned to the fermentation stage by switching-off the aeration, inoculating the fermentation microbe seed and changing the fermentation parameters. The method was applied to the productions of chiral L-lactic acid, ethanol, and sugar acids from wheat straw after dry acid pretreatment, enzymatic saccharification, simultaneous saccharification, and co-fermentation. This pH peak value can be used as a timely, easily visible, and detectable indicator of submerged liquid biodetoxification completion with rapid and complete removal of inhibitors and negligible loss of fermentable sugars.