Potassium (K) is known for alleviating the negative effects of abiotic stresses on plants. To explore the functions of K in controlling reactive oxygen species (ROS), antioxidant activities, and osmoregulation in sesame under drought stress, a pot experiment was conducted with three K levels (0, 60, and 120 kg ha^–1, recorded as K0, K1, and K2, respectively) and exposed to well-watered (WW, 75% ± 5% soil relative water content) and drought-stressed (DS, 50% ± 5% soil relative water content) conditions. The results showed that DS stimulated the production of ROS such as increased hydrogen peroxide (H₂O₂), leading to lipid peroxidation as characterized by higher malondialdehyde (MDA) and, consequently, resulting in the decline in relative water content (RWC) and photosynthetic pigments as compared with WW plants. These adverse effects were exacerbated when drought stress was prolonged. Concurrently, K application alleviated the magnitude of decline in the RWC, chlorophyll a, and chlorophyll b, and plants applied with K exhibited superior growth, with the optimal mitigation observed under K2 treatment. Additionally, DS plants treated with K exhibited lower lipid peroxidation, higher antioxidant activities, and increased osmotic solute accumulation in comparison with plants under K deficiency, which suggested that exogenous K application mitigated the oxidative damages and this was more prominent under K2 treatment. Noteworthily, proline and soluble protein, respectively, dominated in the osmotic regulation at 3 and 6 days of drought stress according to the analysis of the quantitative comparison among different osmotically active solutes. Based on the correlation of the aforementioned traits and the analysis of variance on the interaction effects of drought stress and potassium, we propose that superoxide dismutase (SOD), glutathione reductase (GR), and MDA could be critical indicators in balancing ROS detoxification and reproduction. In summary, our studies suggest that optimized K application keeps a balance between the production of antioxidants and ROS and simultaneously affects osmoregulation to alleviate the damage from drought stress.