To support in situ lunar regolith resource utilization for a lunar base Controlled Ecological Life Support System (CELSS), this study selected the nitrogen-fixing cyanobacterium Nostoc commune and halophyte Suaeda salsa (L.) Pall. based on extremophile soil amelioration theory. Three cultivation treatments were established: Nostoc commune monoculture (Group A), co-culture of N. commune and S. salsa (Group B), and S. salsa monoculture (Group C). Stratified sampling (0–0.5 cm surface, 1–1.5 cm middle, 2–3 cm deep) was conducted on day 45 to quantify pH, electrical conductivity (EC), organic matter, total nitrogen, available macro/meso/trace elements, and elemental correlation of plant residues. The results showed that both species survived in lunar regolith simulant; co-culture generated significant synergistic growth promotion for S. salsa. All treatments significantly reduced initial alkaline pH (8.80 ± 0.1). Group A neutralized surface/middle layers most effectively and maximized surface available N/K; Group C exhibited superior surface available P activation; Group B achieved uniform vertical pH/EC regulation and stable carbon–nitrogen residue accumulation. Residual biomass acted as a stable C/N reservoir and altered medium/trace element bioavailability via adsorption and complexation. Group A is suitable for N/K-deficient regolith, Group C for P-limited substrates, and Group B provides comprehensive long-term balanced nutrient supply matching CELSS demands. This study verifies extremophile-based lunar regolith bioremediation and provides differentiated amelioration strategies for lunar in situ resource utilization.