Modern lifestyle has made many live in an unhealthy diet and high working stress. Those conditions make a high possibility for anyone to compromise their immune system. In the past, people have used herbal medicine to maintain their health. One of the medicines from Central Java, Indonesia has been used to reduce neural pain and enhanced the immune system for generations. The formula consists of cloves (Syzygium aromaticum), ginger (Zingiber officinale), and nutmeg (Myristica fragrans) with water as the solvent. In this research, the formula's extract was tested for immunomodulatory activity based on total protein serum in mice (Mus musculus). The extraction process used the reflux method with 10 g of dried sample in 250 ml of water at a temperature of 80°C for 90 minutes. The immunomodulatory test was conducted with five mice groups: the normal group, the positive group with immune booster medicine, and three dosage groups derived from 62.5, 125, and 250 mL of mixed-herb extract for 28 days. The result has shown that the formula's extract has high effectiveness in enhancing the total protein amount, which is 28.11% for the lowest dosage and 37.64% for the most significant dosage. Compared to the positive group, the formula's extract tended to increase globulin rather than albumin. Those significant phenomena have also been proven from ANOVA single-factor analysis with 0.05 of confidence level, resulting in a p-value of 0.001. Therefore, the Indonesian Anti-neurodegenerative mixed-herb water extract has been proven to have a high potential as an immunomodulator.