Under the concerns about chemical fungicide application on plants affecting the environment, climatic changes, human health, and food safety, there is a growing need for applying biological alternatives that grant sustainable agriculture method implementation, plant pathogen inhibition, and plant production increment for food security. Yeasts as microorganisms could be isolated from various environments; many studies revealed that Candida, Saccharomyces, Pichia, and Rhodotorulastrains strains belonging to Saccharomyces genus could be used as biocontrol agents (BCAs) showing antimicrobial activities against many plant pathogens such as Alternaria, Botrytis, Colletotrichum, Fusarium, Monilia, Penicillium, and Rhizopus. Antimicrobial activity mechanisms of yeast-based agents could be explained through different strategies. Chemical antimicrobial agents such as essential oils and chlorine-based compounds could be capsulated utilizing dead yeast cells, and forcing chemicals to get into cells using a vacuum is considered an effective technique for pathogen-controlling and protecting antimicrobial chemicals from hydrolysis and degradation serving chemical concentrations and cost reduction. In another strategy, yeast cells trigger plants to develop pathogen resistance reactions depending on yeast cell wall components that mimic pathogen cell wall components. Also, competition between yeast-based agents and plant pathogens on nutrients and space affected pathogen growth and mycelium formation, negatively resulting in decreasing pathogenicity. In other cases, yeast cells as microorganisms produce enzymes, antioxidants, and toxins that affect pathogen growth directly. Yeast showed a beneficial interaction with plants addressing climate-smart agriculture in which plant productivity was enhanced with reducing chemical application. Implementation of such an approach depends on plant growth promoters’ selection. Recent research focused on yeast application efficiency in enhancing plant growth and productivity under biotic and abiotic stressors accompanied by minimizing chemical applications to achieve sustainability. This chapter discusses yeast (Saccharomyces and non-Saccharomyces) application as a BCA against plant pathologies causing yield losses and both fruit and vegetable spoilage and the potential of yeast application as plant growth promoters.