A fucoidan discovered in the plant Fucus vesiculosus, which lowered the molecular weight of fucoidan, was ideal for its application in the pharmaceutical and food sectors. The aim was to study the impact of ultrasound process parameters on the molecular weight, structure, and antioxidant activity of fucoidan. For optimization of sonochemical process parameters such as temperature, sonication time, and power (intensity), Box–Behnken design (BBD) through the response surface method (RSM) at fixed fucoidan concentrations was compared with a normal process. The outcomes demonstrated that sonochemical treatment significantly decreased molecular weight (Mw) to 318 kDa compared to the control process (815 kDa). Antioxidant activity tests revealed that the sonication treatment significantly increased antioxidant activity (88.9% compared to 65.3% with the control process). Through use of the BBD model, we found that the ideal conditions for degradation of fucoidan were a temperature of 33 °C, sonication time of 40 min, and sonication power of 102.5 W/cm2. Under these conditions, the quadratic model was fitted and the experimental values for Mw and antioxidant activity (318 kDa and 87.4%) were close to the predicated values (316 kDa and 87.9%). According to the findings, sonication treatment is a useful method for lowering fucoidan levels with no observable changes in the monosaccharide units of fucoidan through scanning electron microscope, X-Ray diffraction, and Fourier-transform infrared (FTIR) analysis.