The objective of this work was to optimize different experimental conditions (dye concentration: 90–130 mg/L, salinity: 10–30 g/L, biomass amount: 0.2–0.4 g/L and reaction time: 25–65 min) for the removal of Acid Blue 25 (AB25) dye using Penaeus indicus shell biomass. The experiments were analyzed by central composite design (CCD) at optimum pH of 2. The effect of different concentrations of natural water salinities (10 and 30 g/L) was investigated as important interactive ions. The maximum experimental AB25 dye removal of 95.64% was obtained in the highest salinity concentration of solution, which was in agreement with calculated values based on numerical optimization (R2 = 0.99). The FT-IR characterization confirmed the role of several functional groups on P. indicus shell biomass, which were responsible for the removal of AB25 dye. Thermodynamic parameters for AB25 dye removal were calculated, and negative ∆Go values indicated spontaneous nature of sorption process.