Enzymatic treatment is a promising method to modulate the chemical composition, flavoring substances and to enhance the sensory quality of cigarettes. This study investigates the feasibility of enzymatic treatment in conjunction with co-fermentation with yeast and lactic acid bacteria to improve the quality of low-quality cigarettes. Amylase, flavourzyme, glucoamylase, protease, and their combinations were used for the enzymatic treatment of tobacco-sorghum by using the liquid-state fermentation method. The biochemical components and flavor substances of the fermented products were analyzed. The findings show that amylase and glucoamylase can effectively degrade starch into fermentable reducing sugars, facilitate microbial growth and proliferation, and significantly enhance the levels of flavoring alcohols and esters. Flavourzyme and glucoamylase, either individually or combined with amylase, achieved a more balanced distribution of flavor substances in the products. Additionally, flavourzyme was capable of increasing the content of guaiacol, solanesol, and 2-acetylpyrrole in the fermented products, thereby improving the richness and depth of the cigarette flavor. While the protease treatment group showed fewer flavor substances and higher nicotine content, which was detrimental to the quality of cigarettes. When integrating the fermentation products into low-quality cigarettes, flavourzyme and glucoamylase combined with amylase treatment received higher scores in sensory quality evaluations. This study provides a beneficial strategy for effectively improving the quality of low-quality cigarettes.