The de Broglie wave nature of matter is a paradigmatic example of fundamental quantum physics and enables precise measurements of forces, fundamental constants and even material properties. However, even though matter-wave interferometry is nowadays routinely realized in many laboratories, this feat has remained an outstanding challenge for the vast class of native polypeptides, the building blocks of life, which are ubiquitous in biology but fragile and difficult to handle. Here, we demonstrate the quantum wave nature of gramicidin, a natural antibiotic composed of 15 amino acids. Femtosecond laser desorption of a thin biomolecular film with intensities up to 1 TW/cm 2 transfers these molecules into a cold noble gas jet. Even though the peptide's de Broglie wavelength is as tiny as 350 fm, the molecular coherence is delocalized over more than 20 times the molecular size in our all-optical time-domain Talbot-Lau interferometer. We compare the observed interference fringes for two different interference orders with a model that includes both a rigorous treatment of the peptide's quantum wave nature as well as a quantum chemical assessment of its optical properties to distinguish our result from classical predictions. The successful realization of quantum optics with this polypeptide as a prototypical biomolecule paves the way for quantumassisted molecule metrology and in particular the optical spectroscopy of a large class of biologically relevant molecules.The wave-particle duality of massive matter has become an important aspect of modern physics. Atom interferometry [1, 2] enabled new tests from quantum physics [3] to general relativity [4,5], cosmology [6] inertial sensing [7,8] precision measurements of fundamental constants [9] and forces [10]. The de Broglie wave nature has been shown for large molecules, from fullerenes [11] and molecular clusters [12] up to even high-mass particles [13]. Such experiments probe the quantum-toclassical interface and can even be used as a unique tool to characterize neutral molecules in the gas phase [14,15] with the potential for minimally invasive high-precision spectroscopy [16].However until today, quantum optics with massive native biomolecules has remained elusive in particular due to the challenges in forming stable and intense molecular beams which can be detected with high efficiency and selectivity. Measurements on neutral biomolecules in the gas phase will, however, become valuable as they are solvent-free and allow predicting and evaluating biomolecular electronic properties independent of any coupling matrix environments [17]. Here, we present the first realization of matter-wave interferometry of gramicidin A1, a linear antibiotic polypeptide composed of 15 amino acids with a mass m = 1882 amu = 3.13 × 10 −24 kg, naturally produced by the soil bacterium Bacillus brevis. Interference experiments with this biomolecular prototype brings us a step closer towards quantum experiments with living organisms [18].A typical matter-wave experiment requires an efficient so...