Sweet whey (SW) and nejayote (NE), two agro-industrial wastewaters generated in Mexico, were evaluated as growth media for the cultivation of an alkaliphilic microalgae–cyanobacteria consortium (AMC) which has been reported to contain Nannochloropsis sp. and Pseudanabaena sp. at different initial pH (8, 9, and 10). Phototrophic-mixotrophic cultivation was conducted for 14 d using nejayote with biomass (NEB), sweet whey with biomass (SWB), and a mixture of nejayote and sweet whey with biomass (NESWB) to assess organic matter removal, biomass formation, and metabolite dynamics. The highest chemical oxygen demand (COD) removal was observed in NEB at pH 8, reaching 91.66% and a final COD of 1.04 g L⁻¹. Initial pH values of 9 and 10 maintained alkaline conditions through phototrophic–mixotrophic cultivation, indicating stable biological pH regulation associated with photosynthetic activity. NESWB promoted higher biomass production, particularly at pH 9, suggesting enhanced conversion of organic matter into suspended solids. Moreover, the highest intracellular protein content (30.50 ± 0.90% dry weight) was obtained in NESWB at pH 10, supported by FTIR and SDS-PAGE analyses that indicated changes in protein-related spectral features and band profiles. Biomass reached 4.77 ± 0.80 g L⁻¹ and COD decreased from 14.60 ± 0.70 to 4.18 ± 0.31 g L⁻¹. These results demonstrate that the integration of sweet whey and nejayote under alkaline conditions enables simultaneous wastewater treatment and production of protein-rich biomass, highlighting a sustainable strategy for agro-industrial residue valorization.