Trehalose (Tre) and salicylic acid (SA) are increasingly used to mitigate drought stress in crop plants. In this study, a pot experiment was performed to study the influence of Tre and SA applied individually or in combination on the growth, photosynthesis, and antioxidant responses of sweet basil (Ocimum basilicum L.) exposed to drought stress. Basil plants were watered to 60% or 100% field capacity with or without treatment with 30 mM Tre and/or 1 mM SA. Drought negatively affected growth, physiological parameters, and antioxidant responses. Application of Tre and/or SA resulted in growth recovery, increased photosynthesis, and reduced oxidative stress. Application of Tre mitigated the detrimental effects of drought more than SA. Furthermore, co-application of Tre and SA largely eliminated the negative impact of drought by reducing oxidative stress through increased activities of antioxidant enzymes superoxide dismutase, peroxidase, and catalase, as well as the accumulation of the protective osmolytes proline and glycine betaine. Combined Tre and SA application improved water use efficiency and reduced the amount of malondialdehyde in drought-stressed plants. Our results suggested that combined application of Tre and SA may trigger defense mechanisms of sweet basil to better mitigate oxidative stress induced by drought stress, thereby improving plant growth.