Cadmium (Cd) toxicity and drought stress are cumulatively disruptive to physiological processes in plants. Salicylic acid (SA) has modulatory roles in osmotic balance in plants. Proline, can act as a compatible solute in osmotic adjustment, elevate antioxidative defense system, which improve adversity tolerance in plants. However, how SA regulates proline metabolism under Cd and drought stresses to improve plant tolerance remains largely unknown. To uncover the alleviation mechanism of SA on Salix matsudana Koidz. seedings to Cd and drought stresses, the non-enzymatic/enzymatic antioxidants, proline metabolism, and related enzyme genes were assayed in S. matsudana. This was done under application of Cd (50 µmol·L− 1) and polyethylene glycol (PEG) (at concentrations of 5% (w/v)) to induce drought stress in 1/4 Hoagland solution with the application of SA (50 µmol·L− 1). The results showed that Cd and drought stresses triggered over-accumulation of reactive oxygen species (ROS), and significantly inhibited the growth traits of S. matsudana seedings. Additionally, the combined Cd and drought stresses caused inhibition in root length and plant height. However, SA increased proline accumulation by increasing the activities of ornithine aminotransferase (OAT) and inhibiting the activity of proline dehydrogenase (ProDH), thereby promoting the generation of glutathione (GSH) and ascorbic acid (AsA), and the activities of antioxidative enzymes while also reducing oxidative stress and restoring the growth parameters in Cd and drought-treated S. matsudana. Among the non-enzymatic/enzymatic antioxidative systems, GSH plays a key role in the scavenging of ROS. Accordingly, proline has a vital multifunctional role in exogenous SA-induced Cd and drought stress tolerance.