In this paper we study the main properties of the Ces`aro means of bi-continuous semigroups, introduced and studied by K{u}hnemund in [24]. We also give some applications to Feller semigroups generated by second-order elliptic differential operators with unbounded coefficients in $C_b(R^N)$ and to evolution operators associated with nonautonomous second-order differential operators in $C_b(R^N)$ with time-periodic coefficients.