Soil salinity and freshwater scarcity are among the major global threats to sustainable development owing to their adverse impacts on agricultural productivity especially in arid and semi-arid regions. There is a need to find sustainable alternatives such as salt-tolerant crops and fish to improve people’s livelihoods in marginal areas. This study aimed to maximize the growth and yield of striped catfish (Pangasianodon hypophthalmus) and quinoa (Chenopodium quinoa) cultivated under a biosaline integrated aquaculture–agriculture system. The study was laid in a randomized completely block design of three saline effluent treatments under three replicates: 5000 ppm (T1), 10,000 ppm (T2), 15,000 ppm (T3), and control (T0). Agro-morphological and physiological attributes of quinoa were measured. The crop yield in biomass and mineral element composition was also studied. Additionally, fish growth performance parameters such as feed intake and efficiency, growth, and survival rate were also calculated. Our results indicated that irrigating quinoa with saline aquaculture effluents above 10,000 ppm enhanced the plant growth, yield, and nutrient content of seeds. Furthermore, rearing striped catfish in saline water reaching up to 15,000 ppm did not have adverse impacts on the growth and survival of fish. Overall, integrating catfish and quinoa production under a salinity regime of 10,000 ppm could be a potential solution to ensuring alternative food sources in marginal areas.