Physical pretreatment procedures can significantly influence the quality of food and feed raw materials. To increase the ability to be digested in animals, cassava chips were pretreated by four alternative methods (extrusion, microwave irradiation, gamma irradiation, or NaOH hydrolysis), and then the chemical composition, physicochemical properties, and in vitro digestibility of the pretreated samples were assessed and compared with unprocessed cassava chips (control). The chemical compositions (crude protein, ether extract, neutral detergent fiber, acid detergent fiber, ash, non-fiber carbohydrate, and gross energy) were significantly altered due to the pretreatment methods (p < 0.05). The nutritive profile was qualitatively changed when assessed through Fourier-transform infrared spectroscopy. Some physicochemical properties in association with enzymatic hydrolysis, which include pH, water solubility, water absorption capacity, thermal properties (differential scanning calorimetry), diffraction pattern (X-ray diffractometry), and microstructure (scanning electron microscopy), were significantly changed. In vitro carbohydrate digestibility based on digestive enzyme extracts from Nile tilapia (Oreochromis niloticus) suggests the microwaving method for cassava chips preparation, while microwaving, followed by extrusion or gamma irradiation, was suggested for broiler (Gallus gallus domesticus). There were no differences in the pepsin-cellulase digestibility values tested for the ruminant model. These findings suggest the use of pretreated cassava chips in animal feeding.