Background: In this study, we aim to explore the protective effect of ginsenoside Rh1 against intervertebral disc degeneration (IDD) and the related mechanism. Materials and Methods: IDD model in Sprague-Dawley rats was established and the animals were treated with different concentrations of ginsenoside Rh1 for 4 weeks, after this, the animals were sacrificed and the intervertebral disc of was collected for analysis using quantitative polymerase chain reaction. Western blot analysis was performed for quantifying the expression levels of glycosaminoglycans (GAGs) and Types I and Type II collagen. Moreover, serum samples were collected and the expression levels of some of the inflammatory cytokines such as interleukin (IL)-1 β and IL-6 were evaluated. Next, we collected the nucleus pulposus (NP) cells from the animals and were divided into five groups: control, IDD, treatment groups with different concentrations of ginsenoside Rh1 (10, 20, and 50 μg/mL). After treatment, the levels of IL-1 β and IL-6 in the cell culture supernatant were examined. Then, we performed western blot analysis to quantify the levels of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra-large (BCL-xL), and nuclear factor kappa-B (NF-κB) in different groups. Results: We observed that ginsenoside Rh1 significantly downregulated the expression of type I collagen and upregulated the expression of type II collagen and GAG under in vivo conditions. Moreover, the expression levels of IL-1 β and IL-6 in the serum samples of IDD rats and cell culture supernatant of NP cells isolated from the IDD rats were significantly increased. However, ginsenoside Rh1 significantly increased the levels of Bcl-2 and Bcl-xL and decreased the levels NF-κB both under in vitro and in vivo conditions. Conclusion: Ginsenoside Rh1 demonstrated protective effect against the IDD via regulation of IL-1 β/NF-κB signaling pathway.