As a typical resurrection plant, Selaginella tamariscina exhibits remarkable drought tolerance and resurrection capacity. However, the mechanism of resurrection associated with the alteration of global organic metabolites in S. tamariscina has not been fully elucidated. Objectives of the study were to investigate drought tolerance and recovery capacity of S. tamariscina based on physiological response and to further reveal potential mechanism of resurrection related to changes in antioxidant defense and differential metabolites under drought stress and after rehydration. Results showed that severe drought reduced leaf relative water content from 90–18%, resulting in extreme declines in chlorophyll content and photochemical efficiency as well as a significant increase in malondialdehyde content in leaves, but S. tamariscina plants could rapidly recover within 3 days of rehydration. Superoxide dismutase, peroxidase, and catalase were significantly activated by dehydration and rehydration. In addition, drought-induced accumulations of citric acid and ribitol could be maintained at higher levels in response to rehydration. Although most of organic metabolites were not affected significantly by dehydration (lactic acid, ribonic acid, arabinitol, and erythritol) or decreased sharply under drought stress (glycine, alanine, γ-aminobutyric acid, proline, glyceric acid, vanillic acid, arabinose, and rhamnose), but S. tamariscia has the ability to quickly recover or increase the contents of these organic metabolite after rehydration. Current findings indicated that enhanced antioxidant defense system could be one of the main pathways for acquisition of desiccation tolerance and resurrection capacity, thereby alleviating oxidative damage to S. tamariscina plants. The accumulation of various organic metabolites played critical roles in underlying mechanism of resurrection due to their positive function associated with osmotic adjustment, osmoprotection, antioxidant, and energy metabolism.