Abstract: This study addresses the issues of poor water solubility and tendency to aggregate of 4-hexylresorcinol (4-HR) by preparing a β-cyclodextrin/4-hexylresorcinol inclusion complex (β-CD@4-HR) via the co-precipitation method. The structural characteristics of the complex were systematically analyzed using multiple characterization techniques. Using Litopenaeus vannamei as the subject, the preservative effect of β-CD@4-HR immersion treatment during 4 ℃ refrigeration was comprehensively evaluated through the analysis of typical freshness indicators, microbial determination, and sensory evaluation. The results showed that β-CD and 4-HR formed a stable inclusion complex at a 1:1 molar ratio, with an inclusion rate of 69.8%. Scanning electron microscopy (SEM) revealed that the surface morphology of the inclusion complex became regular and smooth. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses indicated that 4-HR existed in an amorphous state within the β-CD cavity. Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (¹H NMR) confirmed the interaction between the two via hydrogen bonding. Molecular docking further demonstrated that β-CD and 4-HR had the lowest binding energy (−4.376 kcal/mol), indicating the most stable structure. After inclusion, the water solubility of 4-HR significantly improved (saturation solubility reached 338 mg/mL), and in vitro release exhibited sustained-release characteristics. Moreover, the free radical scavenging ability was superior to that of free 4-HR. In the preservation of Litopenaeus vannamei during 4 ℃ refrigeration, β-CD@4-HR effectively inhibited melanosis, delayed texture deterioration, reduced polyphenol oxidase (PPO) activity, suppressed pH increase, controlled the rise in total volatile basic nitrogen (TVB-N) and thiobarbituric acid reactive substances (TBARS) values, and significantly inhibited the growth of total viable count (TVC). The overall preservative effect was superior to that of the free 4-HR group and the control group. Therefore, water-soluble β-CD@4-HR is a highly promising antioxidant preservative for aquatic products.