The industrial and small-scale processing of plant-based food materials is associated with by-products that may have a negative impact on the environment but could add value to bread-based products. The bioactivity of plant-based food by-products, their impact on the properties of functional bread, and their bioavailability/bioaccessibility leading to potential health effects when consumed was reviewed. Plant-based food by-products which may be added to bread include rice bran, wheat bran, corn bran, grape pomace/seed extract, tomato seed/skin, and artichoke stems/leaves. These by-products contain high concentrations of bioactive compounds, including phenolics, bioactive peptides, and arabinoxylan. Pre-treatment procedures, including fermentation and thermal processing, impact the properties of plant-based by-products. In most cases, bread formulated with flour from plant-based by-products demonstrated increased fibre and bioactive compound contents. In terms of the sensory and nutritional acceptability of bread, formulations with an average of 5% flour from plant-based by-products produced bread with acceptable sensory properties. Bread enriched with plant-based by-products demonstrated enhanced bioavailability and bioaccessibility and favourable bioactive properties in human blood, although long-term studies are warranted. There is a need to investigate the bioactive properties of other underutilised plant-based by-products and their potential application in bread as a sustainable approach towards improving food and nutrition security.