Judicious application of saline water except for critical growth stages, could be the only practical solution to meet the crop water demand in arid and semi-arid regions, due to limited access to freshwater, especially during dry winter months. A field experiment was conducted to study the effect of tillage [conventional (CT), reduced (RT), and zero (ZT)], rice straw mulch and deficit saline-water irrigation in wheat (100, 80 and 60% of wheat water requirement, CWR) followed by rainfed sorghum on soil properties and the yields of the cropping system. Yields of both the crops were comparable between RT and CT, but the wheat yield was reduced in ZT. The RT, mulching and deficit saline irrigation in wheat season (60% CWR) increased the sorghum fodder yield. Olsen’s P (8.7–20.6%) and NH4OAc-K (2.5–7.5%) increased in RT and ZT, respectively, over CT under both the crops. Deficit irrigation reduced soil salinity (ECe) by 0.73–1.19 dS m−1 after each crop cycle, while soil microbial biomass C (MBC) and N (MBN), dehydrogenase, urease and alkaline phosphatase reduced with an increase in ECe. The α-glucosidase, MBC, ECe, KMnO4oxidizable N, and urease were identified as major contributors in developing the soil health index. Deficit irrigation (60% CWR) and rice straw mulching under ZT and RT showed higher values of soil health index. Overall, deficit saline-water irrigation under reduced tillage and straw mulching had the greatest potential in maintaining soil health, saving fresh irrigation water without affecting the productivity of the sorghum-wheat system in the semi-arid regions of India. Results also demonstrated that salt affected areas of arid and semiarid countries can replicate the protocol for indexing and screening of soil health indicators to assess the sustainability of a cropping system. This integrated management based on the nature of the available resources also provided a practical approach to achieve the target of land degradation neutrality and land restoration.