Aloe vera is an economic crop due to the presence of a gel-like substance inside the leaves, which contains polysaccharides, vitamins, proteins, fats, and amino acids. There is an ongoing need for this plant and its products for diverse food and pharmaceutical industries. To meet good agricultural practices, we studied the effect of manure application (0%, 10%, and 20% of v/v of soil) and foliar application with distilled water, salicylic acid (SA, 13.8 mg L−1 equivalent to 100 µM), cerium oxide nanoparticles (CeO2-NPs, 50 mg L−1), and cerium oxide salicylic acid nanoparticles (CeO2: SA-NPs; 100 µM + 50 mg L−1) on the growth and physiological responses of Aloe vera, and a factorial experiment was arranged based on a completely randomized design with three replications at Azarbaijan Shahid Madani University, Iran. The results showed that foliar application of CeO2: SA-NPs with the soil-based application of 10% and 20% manure increased plant dry weight and aloin content. The highest harvest index, economic yield, shoots-to-roots ratio, gel dry weight, chlorophyll a and b content, phenolics content of gel, and leaf and gel flavonoids’ content, as well as potassium, magnesium, zinc, and iron content, were obtained by the CeO2: SA-NPs × 20% manure treatment combination. The 10% and 20% manure and foliar application with CeO2-NPs, SA, and CeO2: SA-NPs increased the phenolics content of leaves compared to the control. Manure application (20%) positively affected the plant’s phosphorus content. The results revealed that co-application of soil-based cow manure and foliar CeO2: SA-NPs stimulated the growth and physiological responses of Aloe vera, and the results would be helpful to the agricultural extension sections and pioneer farmers.