The biomass obtained after the extraction of forskolin from the roots of Coleus forskohlii was evaluated as a substrate for the production of acetone-butanol-ethanol (ABE). The spent biomass constituting more than 90% of the raw material showed 50–70% carbohydrates with starch and cellulose being the major constituents. This study was undertaken to optimize enzymatic hydrolysis of C. forskohlii roots for maximum release of fermentable sugars and subsequent fermentation to ABE. The root biomass was hydrolyzed using the Stargen® 002 and Accellerase® 1500. Cocktail of both enzymes (16U Stargen® 002 and 60 FPU Accellerase® 1500) could produce 41.2 g/l of total reducing sugars (glucose equivalent to 32.33 g/l). The production of ABE was optimized in a batch fermentation using Clostridium acetobutylicum NCIM 2877. The maximum ABE production using the root hydrolysates was 0.55 g/l. Pretreatment with lime and Amberlite XAD-4 increased the production of total solvent to 5.33 g/l.