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Aim: This study aimed to compare the antioxidant and anti-inflammatory properties of Sparassis crispa (S. crispa) extracts prepared using different extraction methods and to evaluate how extraction conditions influence bioactive component profiles and biological activities. Methods: S. crispa was extracted using hot water (SC-HWE), high-temperature and high-pressure water (SC-HPWE), and 70% ethanol (SC-EE). Total polyphenol and flavonoid contents, β-glucan content, and antioxidant activities [2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD)-like activity, and catalase-related activity] were evaluated. Anti-inflammatory effects were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 (murine macrophage cell line) macrophages by measuring cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine [interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)] production using enzyme-linked immunosorbent assay (ELISA). Cytokine levels were expressed as a percentage of the LPS-treated control. Results: Extraction methods significantly affected the composition and bioactivities of S. crispa extracts. SC-EE exhibited the highest total polyphenol and flavonoid contents and showed higher DPPH radical scavenging activity and NO inhibitory effects. SC-HPWE contained the highest β-glucan content and demonstrated superior FRAP values along with notable NO inhibitory activity. All extracts reduced LPS-induced IL-1β, IL-6, and TNF-α production; IL-1β showed greater responsiveness to extract treatment, whereas TNF-α exhibited relatively modest changes. At higher concentrations, the suppressive effect on cytokine production was attenuated, indicating a modulatory rather than a strictly monotonic response. Under the present experimental conditions, quercetin showed a limited reduction in cytokine production. Conclusions: These results demonstrate that S. crispa extracts exhibit extraction method-dependent antioxidant and anti-inflammatory activities. The observed effects may reflect the combined contributions of phenolic compounds and β-glucan rather than a single bioactive component. S. crispa extracts may serve as promising natural materials for functional applications related to oxidative stress and inflammation regulation.