We present an analysis of the 700ks Chandra ACIS-S observation of the field around the radio galaxy J1140-2629 (the Spiderweb Galaxy) at z=2.156, focusing on the nuclear activity in the associated large-scale environment. We identified unresolved X-ray sources in the field down to flux limits of 1.3x10^-16^ and 3.9x10^-16^erg/s/cm^2^ in the soft (0.5-2.0keV) and hard (2-10keV) band, respectively. We searched for counterparts in the optical, near-infrared, and submillimeter catalogs available in the literature to identify X-ray sources belonging to the protocluster and derived their X-ray properties. We detect 107 X-ray unresolved sources within 5 arcmin (corresponding to 2.5Mpc) of J1140-2629, among which 13 have optical counterparts with spectroscopic redshift 2.11<z<2.20, and 1 source has a photometric redshift consistent with this range. The X-ray-emitting protocluster members are distributed approximately over a ~3.2x1.3Mpc^2^ rectangular region. An X-ray spectral analysis for all the sources within the protocluster shows that their intrinsic spectral slope is consistent with an average <{Gamma}>~1.84+/-0.04. Excluding the Spiderweb Galaxy, the best-fit intrinsic absorption for five protocluster X-ray members is N_H_>10^23^cm^-2^, while another six have upper limits of the order of a few times 10^22^cm^-2^. Two sources can only be fitted with very flat {Gamma}<=1, and are therefore considered Compton-thick candidates. The 0.5-10keV rest-frame luminosities of the 11 Compton-thin protocluster members corrected for intrinsic absorption are greater than 2x10^43^erg/s. These values are typical for the bright end of a Seyfert-like distribution and significantly greater than X-ray luminosities expected from star formation activity. The X-ray luminosity function of the AGN in the volume associated to the Spiderweb protocluster in the range 10^43^<L_X_<10^44.5^erg/s is at least ten times higher than that in the field at the same redshift and significantly flatter, implying an increasing excess at the bright end. The X-ray AGN fraction is measured to be 25.5+/-4.5% of the spectroscopically confirmed members in the stellar mass range log(M_*_/M_{sun}_)>10.5. This value corresponds to an enhancement factor of 6.0_-3.0_^+9.0^for the nuclear activity with L_0.5-10keV_>4x10^43^erg/s with respect to the COSMOS field at comparable redshifts and stellar mass range. We conclude that the galaxy population in the Spiderweb protocluster is characterized by enhanced X-ray nuclear activity triggered by environmental effects on megaparsec scales.