Biogenic nanoparticles, including extracellular nanoparticles and protein oligomers/aggregates, are attracting increased attention as new biomarkers for disease detection and diagnosis. Extracellular nanoparticles (20–200 nm) are released from biological cells with their composition reflecting cell types and disease status. Protein oligomers and aggregates such as beta-amyloid fibrils are hallmarks of Alzheimer’s disease. We report here a rapid and non-disruptive protocol to extract multi-type bio-nanoparticles in human blood plasma samples. A total of 75 blood samples from healthy controls, patients with colorectal cancer or prostate cancer, and patients with Alzheimer’s disease were analyzed in this study. Using dynamic light scattering, four size populations of biogenic nanoparticles were detected from the extracts: one population with diameters around 100–200 nm that is consistent with extracellular vesicles; one population with diameter around 20–50 nm that may include exomeres, supermeres, lipoproteins; appearance of protein oligomers/aggregates and other nanoparticle complexes around 10 nm and above; and free protein peak around 6 nm. The size distribution curves can be categorized into four patterns, and the relative quantity of different nanoparticle populations can be estimated using the area-under-the-curve ratio or light scattering intensity ratio from the intensity-averaged distribution curve. Larger extracellular vesicles with diameters in the range of 100–200 nm were found to be enriched in patients with advanced-stage colorectal or prostate cancer. Protein oligomers/aggregates and other nanoparticle complexes were detected in patients with Alzheimer’s disease. These results suggest that the size and size distribution patterns of biogenic nanoparticles in blood may reveal disease-specific or relevant information as physical biomarkers for clinical applications.