Metronidazole (MTZ) is a 5-nitroimidazole compound recognized for its dual anti-bacterial and anti-protozoal properties. Non-approved in many countries for farm medicine, due to a lack of data in the literature, the study aimed to determine its pharmacokinetics (PK) in sheep and goats following intravenous (IV) and subcutaneous (SC) administrations. Sheep (n = 5) and goats (n = 5) followed identical study protocols, which involved a two-phase, single-dose (2 mg/kg), cross-over study design with a one-week washout period between treatments. Blood samples were collected over 24 h for analysis. High-performance liquid chromatography (HPLC) was employed for plasma drug quantification. The analytical method exhibited excellent linearity, recovery, and precision. MTZ exhibited relatively rapid elimination in both animal species, notably faster in goats. Goats have shown a significantly higher clearance rate and consequently lower AUC values. This underscores the importance of considering species-specific differences in drug metabolism and clearance when prescribing medications for small ruminants. Recognizing the pivotal role of AUC/MIC in predicting MTZ efficacy, a dosage adjustment between these two animal species may be necessary to ensure optimal therapeutic outcomes. The bioavailability was relatively high in both animal species, suggesting the potential of SC administration as a practical approach in small ruminants, akin to recent trends in human medicine regarding MTZ administration. Additional research is needed to thoroughly assess the in vivo effectiveness of MTZ in diseased sheep and goats, including PK studies after multiple doses, to establish an appropriate dosing regimen for these animals.