The present study deals with the application of artificial intelligence techniques coupled with Box–Behnken (BB) design to model the processparameters for biosorption of cadmium using live Spirulina (Arthrospira) spp. as adsorbent in open race way pond with Zarrouk medium. Thebiomass concentration of Spirulina spp. decreased to half at 4 ppm Cd (II) after 8 days. Based on the LCt50 values, 3.69 ppm (8th day),Spirulina (Arthospira) maxima showed maximum tolerance. Considerable growth and bioaccumulation of Spirulina spp. is observed below1 ppm and tolerant up to 3 ppm. The cadmium adsorption on Spirulina spp. showed good correlation (R2 = 0.99) when applied to Freundlichequation and data fit into pseudo second order kinetics. A four factorial, three blocks and three level Box–Behnken design with initialconcentration (1 ppb to 5 ppb), biosorbant dosage (0.1 gdw to 0.2 gdw), agitation speed (12 rpm to 16 rpm) and pH (6 to 8) as independentvariables and percentage adsorption as dependent variable were selected for study. The data were further processed using artificial neuralnetwork model and DIRECT algorithm for better optimization. The final Cd (II) concentration of <0.5 ppb was achieved with 1 ppb initialconcentration under optimal conditions. A continuous desorption process was also developed for removal of cadmium from Spirulina (Arthrospira)sp.