There is a general drive to reduce pesticide use owing to the potential negative effects of pesticides on the environment and human health. The EU Commission, for example, through its “Farm to Fork Strategy,” has proposed to decrease the use of hazardous chemical pesticides by 50% by 2030. In addition, smallholder farmers in low-income countries do not always follow pesticide safety precautions. This necessitates the introduction of low-risk crop protection strategies also suited for these farmers. Agricultural biologicals can substitute for, or at least partially replace hazardous chemical pesticides. While the market for and use of biologicals is growing quickly in industrialized countries, this practice remains limited in sub-Saharan Africa. To understand the reason behind the low adoption of biologicals, this study examined the knowledge, attitudes, and practices toward biologicals among 150 smallholder farmers in the Chole district in Ethiopia. All farmers used chemical pesticides and/or inorganic fertilizers to protect crops, improve yields, and comply with government regulations. The use of biologicals was, however, restricted to one group of biologicals, bio-fertilizers, which approximately 60% of farmers used, and no use of biologicals for plant protection was reported. Even though the understanding of the concept of biologicals was deemed high among respondents, the majority (90%) did not identify biologicals as safer alternatives to conventional agricultural inputs. More than half of the respondents (54%) did not recommend biologicals as safer alternatives to their colleagues. Nevertheless, even if the responding farmers did not perceive biologicals as risk-free, they had a positive attitude towards biologicals when it came to producing healthy food and increasing crop yields and incomes. In comparison to the positive attitude, farmers’ knowledge and practice of biologicals were generally low; thus, efforts are needed to create awareness among farmers.