The protein-rich liquid resulting from the deproteinization step of the chitin/chitosan production process is proposed as a novel wastewater bio-coagulant. The raw material for producing the bio-coagulant is the crab shell contained in discarded fishery by-products. The protein content of the liquid, determined by OPA assay, was 31.6 mg/L. FTIR spectra proved the presence of chitin, and SEM images showed the presence of a nanoparticulated chito-protein complex in the liquid. Coagulation tests were performed with fisheries wastewater, in which the influence of different parameters, such as the bio-coagulant dose, the pH, the agitation speed, and the settling time, on the effectiveness of the bio-coagulant were investigated. Since different parameters with values in wide ranges may affect the fisheries wastewater treatment by the use of the new liquid bio-coagulant, a multicriterial optimization analysis based on Box-Behnken and response surface method (RSM) was applied. The optimal removal degrees, in terms of turbidity (98.91%), BOD5 (92.05%), and COD (78.92%) were achieved at a bio-coagulant dosage of 17.5 mL/L of fish processing wastewater (FPW) at pH 11.3 and temperature of 25°C. A good fit resulted from the experimental data, the Box-Behnken regression models, and response surface-calculated data. The results revealed new bio-coagulant effectiveness similar or superior to the commonly used chemical coagulants (ferric chloride, aluminum sulfate) and even to commercial chitosan. The obtained data indicate that the new natural liquid bio-coagulant is environmentally friendly and suitable for fisheries wastewater treatment.