Abstract: To investigate the effect of baicalin (BAI)-loaded cross-linked lipoic acid nanocapsules (BAI@cLANCs) against hydrogen peroxide (H₂O₂)-induced senescence in human umbilical vein endothelial cells (HUVECs), this study examined the toxicity of BAI@cLANCs on HUVECs by MTT method. The cell nuclear staining, SA-β-gal staining, and MTT methods were used to assess the optimal concentration of H₂O₂-induced senescence in HUVECs. The cellular uptake of BAI@cLANCs was evaluated using fluorescence microscopy imaging and flow cytometry. The proportion of cellular senescence was determined by SA-β-gal staining. The level of reactive oxygen species (ROS) in senescent cells was detected by fluorescence microscopy imaging and multifunctional microplate reader. The content of malondialdehyde (MDA) in cells was detected by lipid oxidation detection kit, and the cell cycle was analyzed by flow cytometry with propidium iodide staining. The results showed that BAI@cLANCs had no significant effect on the growth of HUVECs in the range of BAI at 2.80−112 mmol/L. 200 μmol/L and 25 minutes were the ideal conditions for H₂O₂-induced senescence of HUVECs. cLANCs as drug delivery carriers significantly enhanced the uptake efficiency of BAI in HUVECs. Compared with the normal group, the H₂O₂ model group showed decreased cell viability, increased positive SA-β-gal staining rate, increased ROS and MDA content, as well as increased percentage of cells blocked in S phase and decreased cells entering G₂/M phase. Compared with the H₂O₂ model group, BAI, cLANCs, BAI + cLANCs, and BAI@cLANCs groups showed increased cell viability, decreased positive SA-β-gal staining rate, decreased ROS and MDA content, decreased percentage of S-phase cells, and increased cells entering G₂/M phase, with the best anti-aging effect in the BAI@cLANCs group. In summary, the results above showed that both BAI and cLANCs have anti-aging properties. With cLANCs as drug carriers, the anti-aging benefits of BAI@cLANCs are synergistic and can effectively delay H₂O₂-induced senescence of HUVECs.