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Ketamine-Assisted Therapy (KAT) presents a promising alternative for addressing mental health challenges, particularly in treatment-resistant conditions, yet little exists in the literature guiding its implementation in an Indigenous context, for Indigenous participants, or describing culturally adapted delivery models. This paper presents insights and lessons learned from a collaborative pilot program between Siksika Health Services and ATMA CENA to design and deliver a culturally responsive KAT program within the Siksika First Nation in Alberta Canada. The initiative aimed to explore the feasibility and therapeutic impact of KAT in an Indigenous healthcare setting, while also being conscious of cultural relevance and opportunities for continued clinical and quality improvement of the program. The pilot followed a five-phase approach: collaboration, knowledge acquisition, lived experience, data collection, and follow-up. Recruitment resulted in 6 participants completing care (3 Indigenous and 3 non-Indigenous). Findings demonstrated notable improvements in symptoms of depression, anxiety, and PTSD, with participants reporting increased emotional regulation and stronger cultural connections. Cultural elements including shared meals, traditional decor and blankets, community orientation, and a mid-program break for cultural events, were central to participant reported safety, trust, and meaning making. Notably, the Indigenous and non-Indigenous participant groups, who were treated together, reported comparable gains in safety, trust, and mental, emotional, and spiritual well-being. These shared outcomes suggest the model may hold relevance for reducing inequities in group KAT delivery. Challenges and lessons learned included need to address stigma and systemic influences experienced by Indigenous participants, barriers affecting timely intention setting and integration therapy, and overcoming logistical barriers when working in rural First Nation environments. This pilot program implementation underscores the importance of culturally responsive mental health interventions and highlights key considerations for expanding psychedelic-assisted therapies in Indigenous communities.