Spermine (SPM) and salicylic acid (SA) are plant growth regulators, eliciting specific responses against salt toxicity. In this study, the potential role of 30 mgL−1 SPM and/or 100 mgL−1 SA in preventing salt damage was investigated. Wheat plants were grown under non-saline or saline conditions (6.0 and 12.0 dS m−1) with and without SA and/or SPM foliar applications. Exogenously applied SA and/or SPM alleviated the inhibition of plant growth and productivity under saline conditions by increasing Calvin cycle enzyme activity. Foliage applications also improved ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase activities, which effectively scavenged hydrogen peroxide and superoxide radicals in stressed plants. Furthermore, foliar treatments increased antioxidants such as ascorbate and glutathione, which effectively detoxified reactive oxygen species (ROS). Exogenous applications also increased N, P, and K+ acquisition, roots’ ATP content, and H+-pump activity, accompanied by significantly lower Na+ accumulation in stressed plants. Under saline environments, exogenous SA and/or SPM applications raised endogenous SA and SPM levels. Co-application of SA and SPM gave the best response. The newly discovered data suggest that the increased activities of Calvin cycle enzymes, root H+-pump, and antioxidant defense machinery in treated plants are a mechanism for salt tolerance. Therefore, combining the use of SA and SPM can be a superior method for reducing salt toxicity in sustainable agricultural systems.