Safety of students in public secondary schools is a matter of concern globally. In Kenya, a number of students in public boarding secondary schools do encounter tragedies ranging from death of students during infernos in schools, students falling sick due to food poisoning or poor hygiene, attack of students by the community and porous school gates which enables strangers to enter in the schools leading to stealing of school property and attack on the students. In 2008, the Government of Kenya launched Safety and Standards manual in both public schools and private schools. Implementations of these standards were expected to make students secure in these schools. However, from 2009 to 2018, there were a number of reported cases of food poisoning, closure of schools due to community threats, loss of lives of students and properties worth millions of shillings in arson cases, diseases caused by poor hygiene and many others which were unreported. The objective of the study was to determine the effect of health and hygiene safety guidelines on students’ safety in public boarding secondary schools in Homa Bay County. The study revealed that physical health and hygiene safety guidelines had significant effect on students’ safety as they accounted for 53.8% of the variation in students’ security. The study also established that health and hygiene safety guidelines had strong and positive effect on students’ safety. The study recommended that school principals should strive to fully implement these safety guidelines to enhance students’ safety in Homa bay County, Kenya. The study may be useful to policy makers and stakeholders in the Ministry of Education in developing more diversified strategies to enhance students’ safety in public boarding secondary schools in Kenya.