A new phenomenological model, based on a second order dissolution kinetics, was developed for the alkaline removal of non-collagenous protein (NCP) from the skin of Nile tilapia (SNT). This model allows estimating the liquid concentration of NCP in terms of temperature, skin size, NaOH concentration and time. This model was fitted with 135 experiments averaging a R2 of 0.99. The root-mean-square deviation and the mean-absolute-percentage error of the model were 0.0041 and 3.15%, respectively. The Arrhenius-activation energy was 15-122 kJ mol-1. Multi-objective optimization led to the highest NCP extraction (NCPE) of 24.3% and to the lowest loss of collagen (LC) of 1.3%, with R2 coefficients of 0.98 and 0.92, respectively. Ultimately, SNT deproteinized under optimal conditions was subjected to acid extraction and purification. FTIR and SEM analyses indicated that the product was a Type I collagen that could be used in the pharmaceutical industry.