Rising environmental concerns associated with the domestic use of solid biofuels have driven the search for clean energy alternatives. This study investigated the in vitro toxicological characteristics of PM 2.5 emissions from residential biomass pellet burning using the A549 epithelial cell line. The potential of modern pellet applications to reduce PM 2.5 emissions was evaluated by considering both mass reduction and toxicity modification. PM 2.5 emissions from raw and pelletized biomass combustion reduced cell viability, indicative of acute toxicity, and also protein expression associated with epithelial barrier integrity, implying further systemic toxicity, potentially via an oxidative stress mechanism. Toxicity varied between PM 2.5 emissions from raw biomass and pellets, with pelletized straw and wood inducing cytotoxicity by factors of 0.54 and 1.30, and causing epithelial barrier damage by factors of 1.76 and 2.08, respectively, compared to their raw counterparts. Factoring in both mass reduction and toxicity modifications, PM 2.5 emissions from pelletized straw and wood dropped to 1.83 and 5.07 g/kg, respectively, from 30.1 to 9.32 g/kg for raw biomass combustion. This study underscores the effectiveness of pelletized biomass, particularly straw pellets, as a sustainable alternative to traditional biofuels and highlights the necessity of considering changes in toxicity when assessing the potential of clean fuels to mitigate emissions of the PM 2.5 complex.