The aim of this investigation was to study the interaction between the bacterial wilt pathogen Ralstonia solanacearum and potato Solanum tuberosum plants in relation to plant growth, secondary metabolism and antioxidant system in response to compost application. Single potato eyepieces were germinated and grown in pots containing sandy soil with or without compost at a rate of 7.5 g kg−1 soil. Non-compost- and compost-treated plants (CTP) were inoculated with R. solanacearum 21 days after planting and then were subjected to biochemical analysis and growth parameters determinations after 14 days of inoculation. The obtained results revealed that pathogen infection caused a remarkable decrease in plant growth related parameters and an increase in disease incidence. However, compost substantially improved plant growth and decreased disease incidence. Data also indicated that there were significant increases in salicylate (SA), phenolics, flavonoids, lignin, and DPPH (2,2-diphenyl-w1-picrylhydrazyl) activity in infected CTP compared with infected non-CTP. In addition, other biochemical indicators of potato enzymatic activities of glucose-6-phosphate dehydrogenase (G6PDH), shikimate dehydrogenase (SKDH), phenylalanine ammonia-lyase (PAL), cinnamic alcohol dehydrogenase (CADH), polyphenol oxidase (PPO), and guiacole peroxidase (GPX) in infected CTP were significantly higher than those in the infected non-compost-treated ones, indicating induction of critical metabolites playing major roles in plant defense to pathogen. Taken together, the results suggested that compost provides effective protection against the Ralstonia bacterial pathogen via stimulating growth and inducing production of secondary metabolites