The present study is aimed to investigate whether ascorbate-glutathione cycle (AsA-GSH cycle) or thiol metabolism is involved in the regulation of arsenate (As(V))-induced oxidative stress and tolerance in ridged Luffa seedlings. As(V) significantly (p < 0.05) declined the growth of Luffa seedlings which was accompanied by the enhanced accumulation of As. The enhanced accumulation of As in tissues declined total protein and nitrogen contents and photosynthesis, and increased the accumulation of reactive oxygen species (ROS). The enhanced levels of ROS cause damage to lipids and proteins as indicated by the increased contents of malondialdehyde (MDA) and reactive carbonyl groups (RCG). The components of AsA-GSH cycle such as ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, and reduced ascorbate were downregulated, while glutathione reductase and glutathione were upregulated by As(V) stress. Thiol metabolic enzymes such as cysteine synthase, γ-glutamylcysteine synthetase, and glutathione synthetase, and compounds such as cysteine, glutathione, and non-protein thiols were stimulated by As(V) stress. These results suggest that thiol metabolism plays a key role in mitigating As(V)-mediated further damage to Luffa seedlings, while AsA-GSH cycle components had a little role in imparting As(V) tolerance. The present study provides information regarding the involvement of AsA-GSH cycle and thiol metabolism in imparting As(V) tolerance in Luffa. The results of this study can be utilized for As(V) toxicity management in Luffa while keeping these biochemical components into consideration.