Background The therapeutic utility of Panax notoginseng saponins (Xuesaitong soft capsules) for patients with acute ischemic stroke (AIS) was previously demonstrated through the PANax notoginseng Saponins Treatment of aDults with ischemic stroke in ChinA (PANDA) trial, revealing significant gains in functional independence compared to placebo. However, the related variation of older age accepted as the predictors of poor outcome, in response to Panax notoginseng saponins remains unexplored. Methods We conducted a prespecified analysis of the PANDA trial to evaluate the effect of age on the efficacy and safety of Xuesaitong soft capsules. A multivariable logistic and Cox regression analysis with an interaction term was used to determine whether age (< 65 years vs. >= 65 years) affected the treatment effect. The primary outcome of this study was functional independence at the 3-month follow-up, as indicated by a modified Rankin Scale score (mRS) ranging from 0 to 2. Results Between July 1 th, 2018, and June 30 th, 2020, a total of 3072 patients were recruited from 67 medical centers in China. Of these, 2966 patients were incorporated into the intention-to-treat (ITT) analysis and subsequently categorized into two age-based subgroups: (1) 1788 patients (60.28%) aged less than 65 years and (2) 1178 patients (39.72%) aged 65 years or older. Age significantly influenced the proportion of AIS patients attaining functional independence within three months [aged >= 65 years, adjusted odds ratio (aOR): 3.15, 95% CI: 2.13-4.67, P < 0.0001; aged < 65 years, aOR: 1.84, 95% CI: 1.33-2.54, P = 0.0002; P for interaction = 0.027]. Notably, a significant interaction was detected between age categories and treatment, with a greater likelihood of achieving functional independence among AIS patients aged >= 65 years. Regarding the primary safety outcome, which measured the rate of serious adverse events (SAEs) at 3 months, no significant difference was detected between the treatment and placebo groups across both age categories (aged >= 65 years, aOR: 0.32, 95% CI: 0.06-1.69, P = 0.181; aged < 65 years, aOR: 1.76, 95% CI: 0.41-7.47, P = 0.444; P for interaction = 0.132). Conclusions This prespecified secondary analysis suggests that AIS patients can potentially benefit from Xuesaitong treatment in achieving functional independence, irrespective of age. Furthermore, older individuals may experience more substantial clinical benefits from Xuesaitong soft capsules for AIS.