Low health literacy (HL) has been linked to low self-rated health, reduced efficacy of behaviour change, and challenges in preventing, treating, or managing health conditions. People experiencing homelessness are at risk of poor HL; however, few studies have investigated HL in relation to mental and spiritual well-being among people experiencing homelessness in general, or women experiencing homelessness specifically. This cross-sectional study of 46 women experiencing homelessness in Stockholm, Sweden, recruited during the period October 2019–December 2020, aimed to examine how HL was associated with mental and spiritual well-being among women experiencing homelessness. Participants answered questions about socio-demographic characteristics (age, length of homelessness, education) and digital technology (mobile phone/the Internet) use, in addition to Swedish language versions of three questionnaires administered through structured, face-to-face interviews: the Communicative and Critical Health Literacy Scale, the General Health Questionnaire 12 and the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being. Data were analysed using linear regression, which revealed statistically significant associations between HL and mental well-being (p = .009), and between HL and spiritual well-being (p = .022). However, neither socio-demographic characteristics nor digital technology use were significantly associated with HL. In conclusion, promoting HL may improve mental and spiritual well-being in this vulnerable population. An advisory board of women with lived experiences of homelessness (n = 5) supported the interpretation of the findings and emphasised the need to consider HL in relation to basic needs such as ‘housing first’. Moreover, health information and services should be accessible to people with different degrees of HL.