Astringency is a common issue in squid processing and consumption. Various techniques such as soaking in salt water, adding acids, and using enzymes have been used to eliminate astringency. However, these methods have their limitations, and the search for a better solution is ongoing. In recent years, ultrasound technology has been proposed as an effective method for removing astringency in squid. This study used four proteins, including lysozyme, bovine serum albumin, collagen, and whey protein, to simulate saliva in the human oral cavity. This study aimed to determine the removal effect of squid astringency after saliva soaking and ultrasound treatment. Physicochemical indicators such as polyphenols and flavonoids, antioxidant activity, relative polymerization degree, and solution zeta potential were used as physicochemical indicators. Sensory evaluation and volatile salt nitrogen content were used as quality indicators of squid. The results indicated that artificial simulated saliva treatment significantly reduces polyphenols and antioxidant activity in squid muscle, reduces the content of volatile base nitrogen, eliminates the astringency of squid, and improves the taste and overall quality of squid. The technique of using ultrasound technology and artificial simulated saliva is a scientific and effective method for removing astringency in squid. This method has several advantages over traditional methods, including being a non-invasive method that does not require adding any chemicals, making it an environmentally friendly solution. The use of ultrasound technology allows for removing astringency in a shorter time than traditional methods. Finally, the technique is cost-effective and easily scaled up for industrial applications. In conclusion, using ultrasound technology and artificial simulated saliva treatment is a promising method for removing astringency in squid. The technique effectively removes astringency in squid muscle, improves the taste and overall quality of the squid, and is a non-invasive, environmentally friendly, cost-effective solution that can be easily scaled up for industrial application.