Exposure to ambient particulate matter (PM) with an aerodynamic diameter of < 10 µm (PM10) is a well-established health hazard. Air pollution is commonly associated with human activities (e.g., fossil fuel combustion from traffic and industry), yet vast quantities of PM10 are generated by natural hazard events, such as dust storms and volcanic eruptions, that can affect air quality over wide areas and extended periods. There is increasing evidence that geogenic (earth-derived) particles can induce adverse biological effects upon inhalation, though there is high variability in particle bioreactivity that is associated with particle source and physicochemical properties. In order to contribute to the currently limited knowledge of the health effects of diverse geogenic particles, we investigated physicochemical properties and in vitro biological reactivity of volcanic ash from the April 2021 eruption of La Soufrière volcano, St. Vincent, and two desert dust samples: a standardized test dust from Arizona and an environmentally sampled Gobi Desert dust. We isolated sub-10 µm material from bulk samples using an in-house separation set-up and determined particle size, morphology, mineralogy, surface texture and chemistry to establish if there is an association in observed bioreactivity with differences in particle physicochemical properties. We also assessed particle oxidative potential, which is generally implicated in inflammatory responses to particles, and the presence of adhered microorganisms, which can generate an immune response. Cellular responses to acute particle exposures were assessed in monocultures using two types of cells of the human airways (BEAS-2B bronchial epithelial cells and A549 alveolar type II epithelial cells). Post-exposure (24 h), we assessed the cytotoxic and pro-inflammatory effects by measuring the release into the culture media of LDH and inflammatory mediators/cytokines (IL-6, IL-8, IL-1β and TNF-α), respectively. The results showed that, while similar in bulk chemical composition, morphology and oxidative potential, volcanic ash and desert dust exhibit intrinsically different particle surface textures and chemistry, and variable mineralogical content. We also found that dust from the Gobi Desert is more bioreactive than freshly erupted volcanic ash and Arizona dust, which is possibly linked to the presence of microorganisms (bacteria) and nanoscale fibre-like silicate minerals on the surface of this sample. The outcomes of the study serve to help recognise particle components of natural mineral dusts linked to toxicological outcomes, which has implications for public health and air pollution management