Background <p>People experiencing homelessness (PEH) are amongst the most marginalised populations in the society. Despite facing extreme health inequalities and poorer outcomes than the general population, they are under-represented in clinical trials. Little is hence known about the physical, mental health and social characteristics of PEH as clinical trial participants. Cross-sectoral complex interventions aiming to mitigate health, wellbeing and wider inequalities faced by PEH are urgently needed.</p> Methods <p>This paper reports on baseline characteristics of PEH from the PHOENIx Community Pharmacy multicentre Pilot randomised controlled trial (RCT) with recruitment from community pharmacies in Glasgow and Birmingham, UK. Participants were randomised 1:1 to receive PHOENIx (collaboration between National Health Service pharmacist independent prescribers and third sector workers) intervention in addition to usual care (UC) or UC only. Data were collected using face-to-face patient questionnaires which included validated tools (e.g. Equation&#xa0;5D), direct clinical observations (e.g. blood pressure, grip strength) and healthcare utilisation records (e.g. hospital admissions).</p> Results <p>A total of 100 participants were recruited as planned from five community pharmacies. Participants (<i>n</i> = 99 baseline records for one were lost) were on average 42 years old, mostly white (87, 88%), and male (81, 82%). Most had recently slept rough (57, 58%), were registered with an Alcohol and Drug Recovery Service (79, 81%), and prescribed opioid substitute therapy (74, 75%). A minority reported having a recent street substance-related overdose (15, 15%). Most participants reported one or more chronic physical health condition (83, 85%). Fifteen (15%) participants rated severity of breathlessness as 4. Thirty-four (44%) participants were deemed pre-frail and 43 (56%) as frail. Participants had an average EQ-5D-5L health-related quality of life score of 42.2 (SD 24.7).</p> <p>Seventy-six (77%) participants reported having a mental health condition or difficulty; depression (<i>n</i> = 56, 56%), anxiety (<i>n</i> = 47, 47%), self-harm/suicide attempt (<i>n</i> = 21, 21%). Only half were known to housing/casework services. Moreover, half walked to appointments and a minority of those diagnosed with a blood borne virus were in receipt of treatment. Over three quarters had been imprisoned in the past.</p> Conclusions <p>Baseline characteristics of PEH who participated in the PHOENIx Community Pharmacy pilot RCT demonstrates multiple, complex and unmet health, social and practical needs. The data emphasises the need to engage, support, refer and treat PEH through integrated and bespoke pathways to promote people’s engagement with care, prevent repeat homelessness and early deaths.</p> Trial registration <p>International Clinical Trials Registration ISRCTN88146807. Date of registration 18/07/2022.</p>