Azithromycin and amoxicillin are two different antimicrobial drugs, differing in antimicrobial spectrum, indications, contraindications, and adverse reactions. Azithromycin is a macrolide antibiotic, which exerts antibacterial activity by inhibiting bacterial protein synthesis. In addition to being effective against bacteria such as Aureus and Streptococcus pneumoniae, Azithromycin also possesses strong antibacterial activity against specific pathogens such as Chlamydia pneumoniae and Chlamydia trachomatis. It can be used for the treatment of acute bronchitis, pneumonia, skin and soft tissue infections, genitourinary tract infections caused by sensitive microorganisms. Amoxicillin is a broad-spectrum penicillin drug, through the inhibition of bacterial cell wall synthesis to play a bactericidal role, on the Gram-positive bacteria, Gram-negative bacteria have a strong killing effect on Streptococcus pneumoniae, hemolytic streptococcus, Streptococcus oxysporus, and so on are effective. It can treat respiratory tract infections, genitourinary tract infections, skin and soft tissue infections, typhoid fever, paratyphoid fever, etc. caused by sensitive bacteria. In terms of contraindications, amoxicillin should not be used for those who have a history of allergy to penicillins; azithromycin should not be used for those who have a history of allergy to macrolides such as erythromycin, and it can’t be used for those who have had cholestatic jaundice and hepatic dysfunction with previous use of azithromycin. Azithromycin adverse reactions to gastrointestinal discomfort is the most common, such as diarrhea, nausea, vomiting, abdominal pain, etc., the other can be elevated liver enzymes, allergic reactions and other adverse reactions; amoxicillin after the use of occasional gastrointestinal dysfunction, and even exfoliative dermatitis, urticaria, and other allergic reactions occur. Both drugs should be used under the guidance of a doctor, who will choose the appropriate antibacterial drug according to the patient’s personal situation.