The data described in this article was obtained in an experiment designed for generation of biogas from the anaerobic co-digestion of Fluted pumpkin fruit rind and poultry manure in three phases namely A, B and C. This paper is directly related to a published article "Dahunsi SO, Oranusi S, Efeovbokhan VE, Zahedi S, Ojediran JO, Olayanju A, Oluyori AP, Adekanye TA, Izebere JO, Enyinnaya M (2018). Biochemical conversion of fruit rind of Telfairia occidentalis (Fluted pumpkin) and Poultry manure. Energy Sources (Part A) Utilization and Environmental Effects , 40(23): 2799-2811". This paper presents the data on optimization of important process parameters (temperature, pH, retention time, total solids and volatile solids) for standardization during the production of biogas. The response surface methodology (RSM) and artificial neural networks (ANNs) were both used for the modeling and optimization in this study and the optimal conditions for this process were statistically predicted as temperature of 30.02 °C, pH of 7.90, retention time of 20.03 days, total solids of 5.94 g/kg and volatile solids of 4.01 g/kg. The predicted biogas yield under the above set conditions was 2614.1, 2289.9 and 1003.3 10 −3 m 3 /kg VS for digestions 'A', 'B' and 'C' respectively.