High salinity levels exert detrimental effects on plant growth and development by disturbing photosynthesis, water relations, and nutrient absorption. Different soil amendments are used to lower the adverse effects of soil salinity on plant growth and development. This study investigated the impacts of cottonseed meal (CSM) application as soil amendment on soil enzymes, macro- and micro-nutrients, and phenol, and sugar contents in cotton plants grown on normal and saline soil. Three different CSM levels, i.e., 0 (CK), 40 and 80 Mg ha^-1 were included in the study. Soil amendment with CSM significantly increased soil enzyme activities, organic carbon, and available nutrients, and improved soil structure. Soil amendment with 40 Mg ha^-1 CSM improved dehydrogenase, and urease enzyme activities by 15.38 and 40.51%, whereas amendment with 80 Mg ha^-1 improved the activities of these enzymes by 15.29 and 21.47%, respectively. However, the activity of catalase enzyme was decreased by 32.18 and 48.28% under 40 and 80 Mg ha^-1 CSM amendment, respectively. Soil amendment with 40 Mg ha^-1 CSM to increased N, K, Ca, and Mg contents by 65.90, 52.29, 5.71, 15.79%, and decreased Na content by 28.85%, whereas 80 Mg ha^-1 increased these nutrients by 87.12, 53.63, 10.60, 40.63% and decreased Na content by 4.19%. Similarly, application of 40 Mg ha^-1 CSM significantly increased B and Mn contents in plants by 7.12, 8.6% on saline soil and 1.13, and 10.09% on normal soil. Likewise, while 80 Mg ha^-1 CSM application increased the B and Mn contents by 1.84, and 9.46% on saline soil and 4.0, and 8.94% on normal soil. The application of 80 Mg ha^-1 CSM improved total sugar content by 45.5% in saline soil and 3.97% in normal soil. The total phenol content of the plants was improved by 17.25% in saline soil and 2.9% in normal soil. It is concluded that CSM can be used alone or in combination with other organic amendments such as compost and poultry manure to lower the adverse effects of soil salinity on soil enzymes and nutrient uptake by plants.