Cyanobacteria-mediated wastewater remediation is an economical, efficient, and eco-friendly technology. The present work deals with the bioaccumulation performance of Arthrospira platensis (Spirulina) grown for four cycles in a medium containing nickel mono-and polymetallic synthetic effluents. The metal uptake by spirulina biomass was evaluated using neutron activation analysis. The effects of effluents on biomass production, protein, and phycobiliprotein content were assessed. Metal accumulation in the biomass depended on the effluent composition and metal ion concentrations. Nickel accumulation in the biomass was directly proportional to its concentration in effluents, and maximum uptake (1310 mg/kg) was attained in the Ni/Cr/Fe system. In the same system, biomass accumulated 110 times more chromium and 4.7 times more iron than control. The highest accumulation of copper (2870 mg/kg) was achieved in the Ni/Cu/Zn/Mo system and zinc (1860 mg/kg)—in the Ni/Cu/Zn/Sr system. In biomass grown in the media loaded with nickel and also chromium, iron, copper, strontium, zinc, and molybdenum, a decrease in productivity (on average by 10%) during the first cycle of cultivation and moderate reduction of protein content (by 15–27%) was observed. The presence of metals in the cultivation media inhibited phycobiliprotein synthesis, especially of phycocyanin, and promoted the synthesis of allophycocyanin. The maximum reduction of phycocyanin content was 77%, and the increase of allophycocyanin content—by 45%. Arthrospira platensis may be deemed as bioremediation of nickel-polluted wastewaters of complex composition.