The primary management of SCD relies on orthodox medicine; however, many adults living with SCD also use herbal medicine as an alternative or complementary approach. Limited research exists on how patients perceive the use of herbal medicine within SCD care. This study explored the perceptions of herbal medicine use among adults living with SCD in Ghana. An exploratory qualitative design was employed, and purposive sampling was used to recruit 13 adults with SCD receiving care at the University of Ghana Medical Centre. In-depth, face-to-face, semi-structured interviews were conducted and audio-recorded with informed consent. Data were analysed using thematic analysis. Findings revealed that perceptions of herbal medicine were shaped by personal experiences, family and cultural influences, and interactions with healthcare providers. While orthodox medicine was widely trusted for managing acute crises and preventing complications, herbal remedies were commonly viewed as essential for holistic well-being, symptom relief, and disease prevention. The findings highlight strong social and familial networks that sustain herbal use but also expose limited communication between patients and healthcare providers, often resulting in concealment of herbal practices. Medical pluralism was a prominent feature of participants’ care-seeking behaviour, driven by affordability, accessibility, and cultural identity. Participants expressed a clear desire for open, non-judgmental dialogue and professional guidance on herbal medicine use, emphasising that ongoing engagement with healthcare services is vital for improving disease literacy among individuals with SCD. However, participants’ health literacy does not exclude the use of alternative approaches. Incorporating safe, validated herbal practices into formal healthcare could strengthen patient–provider relationships, build trust, and support holistic management of SCD.