Background: Drought stress restricts cotton production, which causes a considerable loss of cotton yields worldwide. Plant activators improve crop production and ameliorate abiotic stresses. Thus, the effects of plant activators on the genotype of cotton (Gossypium hirsutum L.) Candia, which is resistant to drought, were investigated.Methods: Plants were treated with the plant activators, and then osmotic stress was initiated by 30% PEG 6000 treatment for 13 days. Antioxidant enzyme activities such as superoxide dismutase (SOD), ascorbate peroxidase (APX), and peroxidase (POX) were measured along with growth, relative water content (RWC), osmotic potential, photosynthetic pigments, ion leakage, proline accumulation, malondialdehyde (MDA) content, and reactive oxygen species (ROS).Results: Osmotic stress reduced shoot fresh weight (FW) and osmotic potential but increased root length of Candia. Activator treatment alleviated these effects. Photosynthetic pigment contents and cell membrane permeability were not affected by osmotic stress and activator treatments; proline accumulation and lipid peroxidation levels were enhanced by osmotic stress, but activators alleviated these increments. Activity bands for the isozymes Mn-SOD1, SOD2, and SOD3, as well as the isozyme Fe-SOD, were found in Candia. Osmotic stress elevated APX activity in Candia leaves, while activator treatment decreased it. POX activity was not affected by osmotic stress, but activator treatment decreased POX activity. Osmotic stress-induced accumulation of ROS was lessened by activator treatment.Conclusion: Plant activator treatment reduced the amount of oxidative damage (ROS buildup and lipid peroxidation) caused by drought stress in the Candia genotype.Keywords: Antioxidant system; Cotton; Gossypium hirsutum L.; Osmotic stress; PEG 6000; Plant activators