Herbaceous peony is a perennial flowering plant with strong environmental adaptability and may be a good candidate for culture in arid areas. In this study, the physiological and biochemical responses of two herbaceous peony cultivars to different soil moisture gradients in pots were assessed by analyzing changes in 13 stress-related indices. The drought damage index (DDI) and the contents of malondialdehyde (MDA), soluble sugar, proline, and abscisic acid (ABA) generally increased as drought stress intensified, whereas leaf relative water content (LRWC) decreased, and the contents of soluble protein, indole-3-acetic acid (IAA), the ratio of IAA and ABA, and the activities of four antioxidant enzymes fluctuated. For the leaves, a positive correlation was found between DDI and superoxide dismutase (SOD), MDA, soluble sugar, proline, ascorbate peroxidase (APX), and ABA, but it was negatively correlated with LRWC, peroxidase (POD), and catalase (CAT). In fibrous roots, DDI was positively correlated with MDA, soluble sugar, proline, soluble protein, and ABA but was negatively correlated with SOD, CAT, APX, and IAA/ABA. Principal component analysis and subordinate functions were used to evaluate drought resistance of the two cultivars, with ‘Karl Rosenfield’ showing greater resistance to drought than ‘Da Fu Gui’.