This cross-sectional study aimed to assess the levels of health literacy and the associated factors among the general population living in 2 schistosomiasis-endemic villages in Jiangxi Province, China. Multistage stratified random sampling was used to select participants, and a face-to-face survey was conducted from July to August 2021 to collect participants’ socio-demographic characteristics and levels of overall health literacy (HL) and its 3 subscales: health literacy of basic knowledge and concepts (HL-BKC), health literacy of behavior and lifestyle (HL-BAL), and health literacy of health-related skills (HL-HRS). The Chi-square test and logistic regression models were used to assess the association between socio-demographic characteristics and low HL levels. The prevalence rates of low overall HL, HL-BKC, HL-BAL, and HL-HRS were 84.3%, 61.8%, 82.6%, and 86%, respectively. In addition, no significant differences (P > .05) were noted between the 2 villages regarding overall HL scores and the 3 subscales of health literacy scores. Older age (P < .001), occupation (P < .001), lower educational level (P < .001), and lower annual household income (P < .05) were associated with an increased risk of low HL. Multivariate logistic regression revealed that occupation as a student (OR = 32.289, 95% CI:1.965–530.462, P < .05) and fishermen (OR = 27.902, 95%CI:1.91–407.642, P < .05), lower education level (OR = 0.384, 95%CI:0.149–0.99, P < .05), older age (OR = 5.228, 95%CI:1.458–18.75, P < .001), and lower annual household income (OR = 0.452, 95%CI:0.24–0.851, P < .05) were independently associated with low HL. The prevalence of low HL is high among the population in the schistosomiasis-endemic villages of Jiangxi Province, China. Age, education level, occupation, and annual household income were all independent factors associated with HL levels. Health educational interventions to improve HL should be simultaneously conducted in health promotion work to reduce risky habits.