Soil salinization and sodification have become a considerable threat to sustainable crop production for food security. The efficient biological practice in rice cropping systems, besides modulating saline-sodic soil properties using different amendments, is a necessary tactic to accelerate reclamation. This research aimed to evaluate the potential ameliorative effect of seven organic/inorganic amendments addition on soil properties and the differential responses of three rice genotypes under saline-sodic soil conditions at north of Egypt. A 2-year (2019 and 2020) field experiment was conducted with three rice genotypes, viz., Sakha 106, Giza 179, and Egyptian hybrid rice 1 (EHR1) cultivated in saline-sodic-affected soil amended with seven organic/inorganic amendments, i.e., gypsum, rice straw compost (RSC), farmyard manure (FYM), sulfur, sulfuric acid, calcium superphosphate, and rice husk beside control (unamended soil). This experimental design was a two-factor strip plot with randomized complete blocks with four replications. The morpho-physiological (SPADchlorophyll, water content, leaf area index, and shoot dry weight) and biochemical (catalase (CAT) activity, proline content, carbohydrates, leaf sodium (Na+) and potassium (K+), and Na+/K+ ratio) responses, the associated soil physico-chemical and microbial properties, yield, and its components were determined. RSC, gypsum, or sulfur were the most effective amendments in ameliorating saline-sodic soil properties by significantly reducing electrical conductivity, bulk density, and pH compared to the control and initial soil. Gypsum, RSC, FYM, or sulfur amendments significantly decreased the soil Na+ by 14.2, 11.7, 9.1, and 8.3%; sodium adsorption ratio by 14.9, 12.6, 10.4, and 8.7%; and exchangeable sodium percentage by 13.5, 11.5, 9.3, and 8.2%, respectively, over both seasons compared with control. The organic amendments surpassed inorganic regarding microbial biomass carbon, soil respiration rate, and dehydrogenase activity with the superiority of RSC, FYM, and rice husk over the control treatment. These soil restorations were favorably reflected in morpho-physio-biochemical parameters, yield, and its components for all the tested rice genotypes. The EHR1 is the superior genotype in terms of ion (Na+ and K+) selectivity, CAT activity, possessing lower proline and higher morpho-physiological responses, and productivity. The EHR1 had a considerable physiological effect on saline-sodic soil stress, producing higher yield (7.70 and 7.50 t ha−1) after treating with RSC or gypsum. This indicates that RSC outperforms other amendments in improving saline-sodic soils and enhancing rice productivity. Overall, a single application of rice straw compost (organic amendment) and gypsum or sulfur (inorganic amendment) is a viable sustainable approach for modulating saline-sodic soil’s physico-chemical and microbial properties and for boosting rice’s agronomic and physiological responses in an arid environment.