Introduction: Ischaemia-reperfusion injury (IRI) results in the pathophysiological generation of reactive oxygen species (ROS) with concurrent activation of the complement cascade. This manifests as delayed graft function, which has a significant impact on the longevity of the graft. We aimed to evaluate if ROS scavenging nanoparticles can be used to mitigate IRI related injury during normothermic machine perfusion (NMP). Methods: A randomised, two-stage, preclinical trial was used to assess the impact of poly(propylene sulfide) (polysulfide) nanoparticles (PPS-NPs) on parameters associated with IRI in a renal NMP system (experiment 1, n=6 vs 6). Paired porcine kidneys were randomised to receive either an NP-preservation flush followed by 6 hours of NMP with NP-perfusate, or control preservation flush and standard NMP. Following this, an allogeneic transplant- reperfusion model was used to evaluate if treatment with PPS-NPs improved renal haemodynamics post-transplantation (experiment 2, n=6 vs 6). Kidneys were perfused for 3 hours with or without NP, before being reperfused on a circuit primed with matched blood from genetically different donor pigs for 6 hours, without immunosuppression. Results: In experiment 1, all kidneys perfused well for 6 hours with physiological renal haemodynamics and biochemistry. Kidneys perfused with PPS-NPs had improved regional tissue perfusion on infra-red imaging. In experiment 2, renal haemodynamics were significantly improved during allogeneic reperfusion (post-transplant) after treatment with NP. Complement activation remained significantly lower in treated kidneys with a diminished TNF-a response. This translated into an improvement in tissue integrity. Conclusion: IRI was ameliorated following treatment with NPs during preservation and NMP. This was evidenced by an improvement in renal haemodynamics and diminished inflammatory markers upon reperfusion with allogeneic blood.