Biotechnological advances offer potential opportunities for economic utilization of agro-industrial residues such as coffee pulp. Coffee pulp is a fibrous and mucilaginous residual material obtained during the processing of coffee cherries by the wet or dry process. The coffee pulp contains some amount of caffeine and tannins, which makes it toxic in nature, resulting in the disposal problem, however, the coffee pulp is characterized by its nutritional high-value. To increase the use of the coffee pulp (Arabica or Robusta) in animal feed, these compounds were removed by biodetoxification through solid-state fermentation using Rhizopus oryzae (MUCL 28,168). Temperature, moisture, and inoculum size were those studied parameters that had a significant influence on the decrement of the antiphysiological compounds. It was found that the highest decrease of caffeine (52%) and condensed tannins (52%) was achieved at pH 6.0, temperature 30 °C, initial moisture 70%, and inoculum 1 × 106 spores/g. The results show that with this process a reduction of these compounds can be achieved, allowing efficient use of the coffee pulp in different industries.